Colloid and Interface Science Communications 40 (2021) 100329

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Colloid and Interface Science Communications

journal homepage: www.elsevier.com/locate/colcom

A review on phase-inversion technique-based polymer

microsphere fabrication
Shanthana Lakshmi Duraikkannu a, b, *, Roberto Castro-Muñoz c, Alberto Figoli a
a
Institute on Membrane Technology, ITM-CNR, University of Calabria, Via P. Bucci 17/C, Rende 87030, CS, Italy
b
College of Pharmacy, Al-Kitab University, Altun Kupry, Iraq
c
Tecnologico de Monterrey, Campus Toluca. Av. Eduardo, Monroy Cárdenas 2000, San Antonio Buenavista, Toluca de Lerdo 50110, Mexico

A R T I C L E I N F O A B S T R A C T

Keywords: In this review, the preparation method of polymer microspheres (MCs) by phase-inversion is addressed and
Microspheres discussed in detail. An interesting advantage of MCs prepared by the PI method is tailor-made morphology that is
Absorbent a critical factor in separation/adsorption/transport systems. This is relevant since MCs are useful storage device
Phase-inversion
to load chemical, biological components (e.g. drug, enzyme, antioxidant, among others) for physiological and
Membrane
Emulsification
environmental pollution control applications (towards metal ions/organic moieties from different effluents).
Different parameters have been reviewed, such as preparation mechanism, the effect of loading material used (e.
g. chemical and biomaterials) and their morphologies. Microsized range polymeric materials have been identi­
fied as the most suitable in several high-end applications, where the main requirement is a high active surface
area and inert host polymer matrix. Several conventional techniques (physical and chemical) have been explored
for MCs preparation, as well as the most used structured materials for valuable and sensitive components loading.
The current review also compiles the phase-inversion (PI) methodology, as well-adopted membrane preparation
protocol, for MCs preparation and the main parameters that influence in their size, shape and loading concen­
tration. Special attention has been given to summarize the MCs (mimic membrane morphology) preparation and
its application carried out at ITM-CNR in last decade.

1. Introduction polymer composites observed from literature.

Active surface area is always crucial for overall (separation, removal,
A polymer composite is a blend of more than two polymers with among others) efficiency, but today’s interest is shifted towards spher­
different properties, which at a certain proportion allow synergizing ical shaped polymer composites and denoted as microparticles/
features (such as physicochemical, thermal and separation properties) in microbeads/microspheres (MCs). MCs are defined as a spherical-shaped
the resulting material. Herein, individual components in the composite milli-micron size material loaded with known valuable compounds (i.e.
remain together by physical or chemical interactions but retaining their guest molecules) of interest and packed by host (polymer, metal, among
physical or chemical identities and exhibit superiority over the indi­ others) matrix [7–9]. These concepts of MCs are dated back to the report
vidual pristine state [1–3]. Polymer composites are produced in of Bungenberg de Jong and co-workers [10] on substance entrapment
different shapes and sizes according to the application demand by within coacervates. In the 1950s, Barrett K.Green developed a micro­
various methods. To date, polymer composites can be manufactured in a encapsulation process using phase-separation-coacervation, while the
different structure, such as flat sheet, thin-film, microsphere/micro­ first commercial success of MCs was “carbonless copy paper” [11]. In
particle, hollow fibre, nanofibre, nanoparticle, gel, sponge and foams recent decades, microencapsulation process is used in many industries,
[4–6]. Fig. 1. is a cloud-word showing the well-reported morphologies of such as food (e.g. flavors, preservatives, vitamins/nutrients, colorants),

Abbreviations: AOA, 12-acryloxy-9-octadecenoic acid; BMIM, 1-butyl-3-methylimidazolium hexafluorophosphate; MC, Microspheres; NIPS, Non solvent induced
phase separation; O/W, oil/water; PI, Phase-inversion; PEEKWC, polyetheretherketone; PLGA, polyglycolide; PLA, polylactide; PIT, phase inversion temperature;
PES, polyethersulfone; PSF, polysulfone; PSt, polystyrene; PU, polyurethane; SPG, shirasu porous glass; TIPS, Thermal induced phase separation; VIPS, Vapour
induced phase separation; EIPS, Evaporation induced phase separation.
* Corresponding author at: Institute on Membrane Technology, ITM-CNR, University of Calabria, Via P. Bucci 17/C, Rende 87030, CS, Italy.
E-mail addresses: [email protected], [email protected] (S.L. Duraikkannu).

https://doi.org/10.1016/j.colcom.2020.100329
Received 30 July 2020; Received in revised form 6 October 2020; Accepted 20 October 2020
Available online 25 December 2020
2215-0382/© 2020 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
S.L. Duraikkannu et al. Colloid and Interface Science Communications 40 (2021) 100329

pharmaceutical (e.g. antibiotic, bio-cells, medicine, bioactive agent), uniform/controlled size and shape. The review starts with MCs fabri­
chemical (e.g. carbonless copy paper, catalysts, paints, adhesives, cation through physical and chemical methods followed by a detailed
corrosion inhibitors), agricultural (e.g. pesticide/herbicide/fungicide, compilation of phase–inversion using various host-guest molecules, for
growth regulator, supplement for animal feed, veterinary medicine), example polymer-chelating agent. The effect of physical-chemical pa­
cosmetics (e.g. serum, enzyme loaded cream and lotion) and household rameters influencing the final MCs properties, including size, shape,
products (e.g. detergent, antiperspirant) [12–14]. surface nature, internal cross-section, porosity, stability, and applica­
In general, there are two sets of technologies employed for MC tions, are also addressed. This review will also discuss the recent major
preparation and broadly classified as physical and chemical pathways. advancements focused on phase-inversion technology for improving size
The selection method depends on the application, nature of the polymer, and morphology in MCs. Through reviewing the most relevant reports,
type of loaded material, the interaction between host and guest mate­ the current review highlights the future perspectives in terms of
rials, among other parameters. Major chemical routes including phase- exploring this technique further scale-up process.
inversion (PI), coacervation, polymerization (interfacial and in-situ)
and spray drying, electrostatic deposition, membrane emulsification 2. Overview of microspheres (MCs)
falls under physical routes, as shown in Fig. 2.
MCs have promising potential in various sectors, as demonstrated by 2.1. Background
the growing number of publications on their fabrication and terminal
applications. For instance, Fig. 3 represents the publication trend based Milli and micron size range sphere-shaped particles are generally
on the Scopus database using keywords (polymeric microspheres), while produced from synthetic/biopolymers for various applications. Micro­
it secondly shows the impact of using phase inversion for different types spheres or microparticles, having a suitable size, shape, surface struc­
of applications [15,16], where according to the number of publications ture, and morphology, are applied especially in separation science.
it is likely that phase inversion is the most applied protocol. Polymeric MCs can be prepared by two pathways and the selection
Importantly, a large number of articles highlight that polymer method depends on the nature of the application/materials involved.
composites are combining polymers, nanomaterials, and microbial/ Depending on the loaded/immobilized material and placement, it is
green additives-based composites for various range of applications (such usually classified as a mixed matrix or core-shell. MCs are produced
as medicine, environment, water, industries). At this point, it is of great using various types of polymer, natural (bio)/synthetic (organic) with
importance to adopt a popular membrane fabrication method to tailor- different filling materials (as dispersed phase). Filling materials are idle
made MCs according to the final needs in terms of applications and within the host polymer matrix and are readily available for the pro­
loading materials. In this review, particular emphasis is focused on the posed reactions, e.g., taste masking, sustained-controlled release, sepa­
compilation of reports using PI, as the most established technique, for ration of component/detoxification, and adsorption/separation of
tailored polymeric membranes fabrication for MCs preparation [17,18]. pollutants from different effluents. MCs as a carrier for drugs are also
PI is part of coacervation, where MCs are produced by adjusting pH, known as microparticles, a reliable means to deliver the drug to the
temperature, and viscosity/density of polymer solution. It is a chemical target site with specificity and desired concentration at the site of in­
method influenced mainly by the physical-chemical properties of the terest. In the future by combining various other strategies, MCs will find
compound-solvent involved. The advantages of this method are the the central place in novel diagnostics, genetic materials, safe, targeted,
ability to preserve the activity/nature of the encapsulated material in effective in-vivo delivery and supplements as miniature versions of
the matrix (especially in biomedical, pharmaceutical, and food sector), diseased organs and tissues in the body [19–21].
easy to frame lab module (i.e. scale-up), low energy requirement,

Fig. 1. Graphic collage of polymer composites’ morphologies.

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S.L. Duraikkannu et al. Colloid and Interface Science Communications 40 (2021) 100329

Fig. 2. Major methods involved in microsphere fabrication process.

supercritical fluid anti-solvent. Considering its commercial utility and

importance particularly in the medical field, several improvements have
been reported in the MCs preparation, keeping in mind the physiological
value of loaded material (e.g. drugs, enzymes/nutrients, bacterial
strains, etc.). In fact, the disadvantages related to the implementation of
MCs delivery systems for the delivery of therapeutic compounds are
mainly related to the stability of the incorporated bioactive molecules
since the denaturation or degradation can occur leading to loss of bio­
logical activity. Therefore, the design and preparation of MCs is a cur­
rent challenge in the field, in which the researchers should provide ideas
and alternatives towards suitable fabrication protocols to reach the
desired features of the MCs. For example, Zhang et al. (2006) proposed
the microfluidic production of biopolymer MCs with controlled
morphology. Herein, the droplets of the biopolymer aqueous solution
were emulsified in an organic phase containing a cross-linking agent.
Interestingly, polymer gelation was reached in situ (on a microfluidic
chip) by diffusion-controlled ionic cross-linking of the biopolymer,
following the transport of the cross-linking agent from the continuous
phase to the droplets. Such developed protocol was successfully applied
Fig. 3. Publication record on developing polymeric microspheres and uses of
in producing several types of MCs based on polysaccharides (e.g. algi­
phase-inversion technique over the last decade (www.scopus.com, based on nate, κ-carrageenan, and carboxymethylcellulose) [22]. Therefore,
April 23th, 2020). polymer capsules can be efficiently tailored via external gelation and
chemically patterned microfluidic devices [23,24].

3. Phase inversion (PI) technique

2.2. MCs fabrication pathways
Phase inversion technique was classified into four different cate­
MCs fabrication falls under two types, physical and chemical routes.
gories based on the parameter which controls the overall process
Typically, the fabrication method should satisfy few parameters, such as
[25–28].
the ability to incorporate maximum encapsulation/loading (e.g. drug,
enzymes, chelating agents, flavonoids, among others), tailor-made
- Non solvent induced phase separation (NIPS)
shape, size, surface morphology, stability, shelf-life, release (e.g.
- Thermal induced phase separation (TIPS)
active reagents) with good time control, biocompatibility and suscepti­
- Vapour induced phase separation (VIPS)
bility apart from ease of operation, low operation cost, and possible
- Evaporation induced phase separation (EIPS)
macro-level production. Many of the microencapsulation/microsphere
fabrication processes are the modification of the three core techniques:
Non-solvent induced phase separation (NIPS), well-established
solvent extraction/evaporation, phase separation, and spray-drying. But
membrane preparation protocol, where the liquid-liquid demixing and
coacervation is frequently impaired by the residual solvent/coacervat­
solvent-nonsolvent diffusion rate decide the type of morphology,
ing agent in the final products. The use of supercritical gas, as a phase
including dense, porous spongy, symmetric, asymmetric, among others
separating agent, was intensively studied to minimize the amount of
[29,30]. NIPS is extensively used in PI for membrane preparation
potentially harmful residues in the microsphere, resulting in a process
(tailored morphology, pore size and porosity) and polymer/solvent so­
termed, such as precipitation with compressed antisolvent (PCA), gas or
lution upon immersion into coagulation bath (i.e. nonsolvent), as

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S.L. Duraikkannu et al. Colloid and Interface Science Communications 40 (2021) 100329

represented in Fig. 4. During the process, the diffusion of a solvent and Zeng et al. [38] used a low-cost PI method coupled with carbonization to
non-solvent across the interface induces to phase-inversion of polymer prepare carbon-based sorbents (MCs) for oil spill clean-up (Motor oil,
solution followed by solidification (or precipitation). The thermody­ 40% and Toluene, 55%) with five times reuse efficiency. Composite
namic concepts involved in this process have been described by various macroporous zeolitic imidazolate framework-8/polysulfone (ZIF-8/PSF)
mathematical models, especially the relationship between morphology were prepared via single orifice spinneret as an adsorbent for gases (N2,
and phase-inversion conditions (such as temperature, humidity, coag­ CO2) with easy handling and recycling over ZIF-8 particles [39]. Pathak
ulation bath composition, solvent chemical and physical properties) et al. [40] prepared microporous PES polymeric beads in situ phase
[31]. In membrane preparation, the skin layer generally supported by inversion method (see Fig. 5), which were later loaded 2-ethylhexyl
finger or spongy structure which is controlled by diffusion or transport phosphonic acid mono-2-ethylhexyl ester (PC88A) extractant into PES
phenomena. MCs as a sorbent for Am (III) removal from acidic medium (pH 3) with
Similarly, the PI method, which is employed to produce MCs of 10 cycles of reusability.
tailored morphology, is strongly influenced by the operating parame­ Cao et al. [32] reported a facile route to develop hollow polymer
ters. PI technique has been extensively used for the preparation of MCs microspheres by grafting chlorinated polypropylene with methyl
with different cross-section arrangements using chemically synthesized methacrylate, butyl acrylate and acrylic acid via free-radical polymeri­
and biopolymer, exhibiting a variety of applications within the drug zation and neutralized by trimethylamine. The resulting mixture was
delivery, catalysis, organic, inorganic separation, gas transport, slowly diluted with deionized water to initiate PI mechanism which
adsorption. Apart from the preparation method, size and final properties subsequently yielded hollow polymer microspheres. Yang et al. [41]
of MCs also depend on several other parameters, such as operation investigated the significant potential of wet phase inversion process, as a
condition (e.g. transmembrane pressure, disperse phase flow), material final tailor-made based on final applications, to prepare asymmetric
properties (e.g. pore size and hydrophobic/hydrophilic property), phase membrane capsule shells (AM-CSs) loaded with Metoprolol Tartrate and
(e.g. polymer concentration, coagulation bath temperature/concentra­ Nimodipine drugs for release application. The in-vitro dissolution
tion, oil phase, interfacial tension, viscosity, the density of the processed properties of AM-CSs and homogeneous membrane capsule shells (HM-
phases) and loading material nature and concentration. Polymeric MCs CSs) were compared as well. Gelatin-based polyurethane (PU) grafts
with hydrophilic/hydrophobic nature, smooth/rough surface and were fabricated by co-spraying PU and gelatin followed by phase-
porous/dense/spongy morphology have been successfully prepared via inversion. Composite vascular graft SEM images reveal a morphology
PI method [32–34]. The following section addresses the most mean­ difference between PU (microporous) and gelatin-based PU (fibrillar).
ingful reports on preparing MCs based on different types of polymers Interestingly, a cross-linking application confirmed an enhanced tensile
and inorganic materials. strength, elongation capacity in circumferential directions compared
with pristine PU and cell interaction efficiency (gelatin) [42]. Poly­
styrene (PSt) latex particles (in the range of 30–120 nm) were prepared
3.1. MCs-based on synthetic polymers by free-radical polymerization of an oil-in-water emulsion, where sty­
rene droplets obtained via phase inversion temperature (PIT) using
To date, different types of structures have been documented on the amphiphilic comb-like block polymers (polystyrene-b-poly[oligo
resulting MCs. For instance, Torras [35] explored NIPS for polysulfone (ethylene glycol) methyl ether methacrylate]). Hydrophobic PSt block­
(PSF) MCs preparation which involved two crucial steps, PSF droplet chain length influenced critical micelle concentration, micelle aggre­
preparation followed by precipitation. Chen et al. [36] prepared porous gation number and cloud point [43]. It is important to mention that
polyethersulfone (PES) microcapsules with straight open pores by sur­ Shirasu porous glass (SPG) protocol is also a feasible way at obtaining
face dense layer peel-off technique. In a different approach, micropar­ MCs. Typically, SPG allows controlling of microcapsule diameter by
ticle formation was achieved by controlled phase separation of organic monodispersing the emulsion droplets and thus obtaining a well-defined
and aqueous phases and used as electrophotographic toners [37]. Sty­ capsule core [44]. For instance, Kamio et al. reported the preparation of
rene/acrylate and polyester-based microspheres were fabricated by monodisperse crosslinked polymelamine microcapsules via phase
adding anti-aggregation with a low agitation speed of 1000–1500 rpm.

Fig. 4. Graphical representation of the Non-Solvent-Induced Phase Separation (NIPS) [93].

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S.L. Duraikkannu et al. Colloid and Interface Science Communications 40 (2021) 100329

Fig. 5. Schematic of the procedure for preparation of PC88A impregnated polymeric beads. (A) Preparation of a formulation of PES powder and PC88A in 1-methyl-2
pyrollidone (NMP). (B) Drop-wise addition of the formulation in aqueous bath (phase inversion medium). (C) Curing for 24 h. (D) Separation and washing of the
prepared beads. (E) Optical microscope image of the synthesized beads (10× zoom) [40].

separation method. The resulting MCs displayed microcapsule diameter fluid mechanics theoretical prediction. Porous PLGA microspheres
in the range of 5–60 μm [44]. More recently, Qi et al. also utilized SPG exhibited higher adsorption of a short peptide than non-porous micro­
method to fabricate uniform-sized Exenatide-loaded poly(DL-lactic-co- spheres, which confirmed that the morphology was influenced by
glycolic acid MCs [45], which were subsequently tested in vitro release. preparation routes. A latex nanoparticle was obtained by a low energy
The authors concluded that such MCs had a fast release rate together phase inversion composition method to develop templates of monomer/
with excellent hyperglycemic efficacy within the first 14 days. Brij78/water nanoemulsions as a base to develop polymer and copol­
ymer nanoparticles. Different copolymer latexes, such as styrene, butyl
acrylate and methyl methacrylate, were tested with hexadecane (oil
3.2. MCs-based on biopolymers phase) and subsequently applied in textile printing [55].
Thermally-induced phase separation was implemented for the syn­
Today, biopolymers are identified as potential candidate materials thesis of biocompatible poly (L-lactic acid) nanofibrous hollow micro­
for replacing chemically synthetized polymers due to the current green spheres for drug delivery [56]. The effects of propanetriol (PT) volume,
environment-based legislations. Thanks to their specific properties and polymer concentration, dropping rate, stirring speed on particle size and
biocompatibility, these biopolymers have been successfully employed surface morphology were analysed. Generally, an increase in polymer
for multiple applications, such as drug delivery systems, food packaging, concentration (4 wt%), dropping rate of PT and stirring speed, resulted
biomedicine, hydrogels, water treatment, membranes separation pro­ in homogeneous nanofibrous smaller size MCs. In a different approach,
cesses, among others. To date, different types of biopolymers have been calcium phosphate/sodium alginate MCs surface was imprinted by
used according to their original source, including animal (e.g., polylactic bovine serum albumin (BSA) using inverse-phase suspension [52]. Pre­
acid, polyhydroxyalcanoates), vegetable sources (e.g., polyisoprene, viously, (NH4)2HPO4 was added into the sodium alginate aqueous so­
starch, cellulose-based polymers, alginate), bacterial fermentation lution. Surface molecularly imprinted calcium phosphate/alginate
products (e.g., collagen, chitin derivate polymers) [46–50]. Of course, polymer microsphere analysis revealed the characteristics of surface and
due to the final purpose of the MCs, biopolymers are a latent material for interior specific rebinding behaviours.
their preparation. For example, Mi et al. [51] developed a chitin/poly­ Microporous SPG membranes (pore size 5.2 μm) were used for N2
glycolide (PLGA) and chitin/polylactide (PLA) MCs for protein delivery gas-driven extrusion of polystyrene dissolved in chloroform [57]. A
by the wet PI method. In such a study, the selection of non-solvents, PLA/PLGA polymer mixture dissolved in DCM into a continuous
temperature, PLA/PLGA ratio was adjusted to improve the thermody­ aqueous surfactant solution, followed by subsequent solvent evapora­
namic compatibility of the polymer. It is important to point out that the tion [58]. The PLGA microspheres were generated using continuous
protein delivery depended on the balance between hydration rate of phase preferably anionic surfactants (sodium dodecyl sulfate). However,
chitin and degradation of chitin/PLA, PLGA phases, which exhibited a cationic surfactants interacted electrically with the negatively charged
fast release (first phase) followed by slow release (second phase) again a glass membranes and nonionic surfactants were soluble in both the
rapid release (third phase). Macro molecularly imprinted calcium aqueous and DCM so that they did not adsorb sufficiently at the inter­
phosphate/alginate hybrid polymer microspheres were prepared from face. The maximum concentration of progesterone (i.e. 50%) was suc­
sodium alginate and ammonium monohydric phosphate. Here, CaCl2 cessfully loaded into PLA/PLGA without change in size and uniformity.
was rapidly used as a gelling agent in PI suspension for protein By changing SPG membrane pore size for the production of PLA (10%–
imprinting matrix [52]. Mascheroni et al. [53] developed a natural 20% w/w) MCs using DCM (solvent), dodecyl alcohol, or hexadecane (as
antimicrobial delivery system to prevent pathogenic/spoilage bacterial co-surfactant) and the surfactant reduced solution’s hydrophilic nature
growth in food applications. Basically, propolis was loaded into a chi­ by wetting of polar glass pores that yielded homogenous MCs. It was also
tosan matrix using the phase-inversion technique. Ink-jetting (piezo­ observed that the MCs were not perfectly spherical but elliptical and
electric nozzle) coupled with TIPS was used to produce biodegradable hemispherical when made with dodecyl alcohol and hexadecane,
porous MCs [54]. MCs based on synthetic poly (lactic-co-glycolic acid) respectively [58,59]. When dealing with PLGA/PLA microspheres, Qi
(PLGA), polycaprolactone and gelatin produced open interconnected et al. [60] recently presented a compelling current state-of-the-art on
pores with a mean particle diameter (ca. 80–200 μm) compared with

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Fig. 6. SEM view of the microspheres with high interconnection prepared Li et al. [70].

PLGA/PLA microspheres/nanoparticles for drug delivery applications. [68]. Liang et al. [69] prepared PLGA magnetic microspheres with well-
The authors have found out that the most common used process to controlled sizes (in the range of 100–1000 μm) by this method. These
manufacture PLGA/PLA microspheres are mechanical stirring. Never­ MCs were documented to display an ability in liver cancer therapy with
theless, a few innovative and emerging technologies have been devel­ good biosafety.
oped in pilot or production scale over the recent years. Interestingly, Li et al. [70] reported, for the first time, the use of 12-acryloxy-9-
membrane emulsification is recognized by its advantages in terms of octadecenoic acid (AOA) surfactant for the stabilization of double
mild preparation conditions, fast flux, low cost, high repeatability emulsions (W/O/W). The effects of AOA, NaCl concentration, pH, oil
[60–62]. Likewise, such technique has been successfully implemented to polarity, water addition and stirring rate on the stability of double
prepare monodispersed PLGA/PLA MCs [63,64]. Typically, membrane emulsions were analysed. In principle, the average size of these double-
emulsification comprises two types: direct membrane emulsification, emulsion droplets increased from 19.3 to 328.3 μm when the contents of
and premix membrane emulsification [60]. Within direct membrane AOA content decreased from 25.0% to 14.3% based on the oil phase.
emulsification, oil phase is directly pressed through the uniform pores of Subsequently, the authors prepared porous polymer MCs with high
the membrane into aqueous phase creating uniform-sized droplets on interconnection (see Fig. 6) were fabricated by γ-ray initiated poly­
the membrane. Afterwards, the droplets should be detached by shear merization. Here, the MCs were tailored from as-prepared double
force to form uniform oil/water (O/W) emulsion. MCs are then obtained emulsions based on different monomers, such as styrene or n-butyl
after the organic solvent is removed out. For instance, Liu et al. [65] acrylate or methyl methacrylate). The resulting MCs presented average
reported the usage of membrane emulsification to fabricate W/O/W sizes in the range of 9–18 μm, which can be tuned by adjusting the oil
double emulsion. The authors optimized the size of the MCs by selecting compositions and other parameters (such as pH value, AOA concentra­
a membrane with suitable pore size, and confirmed that release tion). Fig. 6 reveals that the MCs possessed internal holes and irregular
behaviour could be tuned by modifying the diameters of MCs [66]. It is interconnecting pores which was attributed to the higher solubility of
important mentioning that higher encapsulation efficiency (ca. 92%) in methyl methacrylate in water, which allowed the coalescence of inner
membrane emulsification can be reached when compared with con­ water droplets and water diffusion between the inner and outer water
ventional techniques (e.g. mechanical stirring) [67]. Among membrane phases [70]. (See Fig. 7.)
emulsification techniques, rotating membrane emulsification is a
modified direct membrane emulsification which has been applied to
manufacture uniform-sized emulsions and polymeric MCS. Herein, the 3.3. MCs-based on inorganic materials
emulsions are also detached from membrane by membrane rotation
[68]. Importantly, as a technique several parameters (i.e. trans­ To date, it is likely that most of the advances on fabricating MCs
membrane pressure, shear rate, dispersed and continuous phase vis­ imply the use of polymeric materials. Differently, phase inversion
cosity) are fundamental for obtaining desired droplets diameter and flux method has been also used to incorporate metal nanoparticle into
polymer composites [71], e.g. Sanchez and co-workers gold

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Fig. 7. Scheme of the single-stage simultaneous process for microspheres preparation developed by Piacentini et al. [61]. (a) Microspheres generation by emulsi­
fication coupled with phase separation induced process.

Table 1
Development works on MCs fabrication at ITM group.
Matrix Microsphere concept loaded or encapsulated compound/method adopted Application/target of study Reference
polymer

PEEKWC Pristine polymeric microsphere Morphological and Dimensional Study [75,76]

PVDF Combined Emulsion and Phase Inversion Technique Morphology and proof of concept (coupling both [77]
technique)
PVDF Ammonium Molybdate catalyst Used as phase transfer catalyst for alcohol to aldehyde [78]
conversion (Selectivity 99.1% and conversion 56%)
PEEKWC Ammonium Molybdate catalyst Heterogeneous catalyst and interphase contactor promote [79]
selective oxidation of benzyl alcohols to aldehydes
PVDF Adsorbents (activated Carbon) Arsenic removal [81]
PSF, PES, PVP (Polyvinylpyrrolidone) Pore former additives, Tailor made porous/non-porous [86]
PEEKWC microspheres
PEEKWC CYPHOSIL101 (Trihexyl(tetradecyl) phosphonium chloride) Evaluation of ionic liquid loading capacity [33]
PES Cyanex 923(Phosphine Oxide) Uranium and Plutonium extraction [82]
PES Membrane emulsification process Size reduction up to 30–60 μm in MCs produced [61]
PES [BMIM][PF6] Phase-inversion coupled with membrane emulsification [84]
process
PEEKWC [BMIM][PF6] Oil-field scale control process [17]
Chitosan Propolis Encapsulation approach [53]
PES TODGA (N,N,N′ ,N′ -Tetraoctyl diglycolamide) Actinides separation [83]
PSF, PES, [BMIM][PF6] (morphology control additive) [BMIM][PF6] evaluation of material morphology [85]
PEEKWC PVPK17 (pore former)
PES Common anion bis-trifluoromethylsulfonylamide ([TF2N] − ) CO2 permeation studies [93]
Cations include: Diethyl-aminoethyl-imidazolium [DEAEBIM], Aminopropyl-butyl-
imidazolium [APBIM], Diaminopropyl-butyl-imidazolium [DMAPBIM]

nanoparticles loaded carbon nanotube/PSF composites. According to AFM. Chen and Ma [74] studied the fabrication of low-melting metal
the authors’ hypothesis, phase-inversion technique can be able to merge particles, such as Bi-Pb-Sn-Cd metal nanoparticles, having an average
water-soluble metallic and semiconductor nanoparticles and quantum diameter of particle size about 0.3 μm, with sodium oleate dispersant.
dots into the CNT/polymer matrix in a one-step process [71]. Poly­
styrene nanoparticles loaded with fluorescent pyrene were prepared by 4. ITM’s research group contributions on phase-inversion based
direct polymerization at PI temperature [72]. An average diameter of microsphere fabrication
the nanoparticles was around 22–30 nm, and the process did not require
any strong stirring or a large amount of surfactant, which is a critical For more than a decade, the implementation and investigation of
parameter for standard mini and microemulsion polymerization. In MCs fabrication have been a scope of study at ITM group, where the
principle, the pyrene loading was confirmed by fluorescence spectra and effect of different additives, as well as process conditions, on the
the superior loading capacity can be translated to different hydrophobic morphology of the resulting MCs has been analysed in detail. For
polymers. Munirasu and Nunes [73] utilized the PI technique to fabri­ instance, Table 1 enlist the most relevant studies in the field. Homoge­
cate asymmetric organic-inorganic porous SiO2-g-PMMA nanoparticles. nous and spherical shape MCs obtained through integration between
Basically, the synthesis implied 3-(dimethylethoxysilyl) propyl-2- non-solvent induced phase separation and pressure extrusion using a
bromoisobutyrate) functionalized silica nanoparticles followed by mono-pore membrane has been explored by ITM group. Initially, Figoli
PMMA grafting using atom-transfer radical polymerization. Asymmetric et al. [75] reported the influence of an oil phase (normally hydrocarbon
porous morphology and nanoparticle assembly were confirmed by SEM, solvent) on polyetheretherketone (PEEKWC) MC surface morphology, i.

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S.L. Duraikkannu et al. Colloid and Interface Science Communications 40 (2021) 100329

e. smooth (using dodecane) or rough (using isooctane). According to a single-stage simultaneous process presenting microdroplet formation
their findings, the changes in the number of carbons influenced the and solidification. Continuous phase coagulation bath composition,
surface tension of an oil phase and thereby developed smoother surface. dispersed phase flux, shear stress and nature of emulsifier on the
Concurrently, a further balance force analysis model was applied to microdroplet size was studied in detail. The resulting PES microparticles
evaluate the relation between PEEKWC capsules size with the droplet of size 30–60 μm presented a smooth spherical surface obtained as a
diameter derived along with the pore mouth [76]. The theoretical free-flowing powder state characterized for its homogenous size
analysis has provided more information about the droplet detachment distribution.
mechanism that occurs during this protocol as a function of membrane The mineral scale is a persistent and expensive problem in the oil
and process parameters. At the end of the PI process, the mono-pore industry. In theory, scale control agents loaded polymer MCs are viable
polyethylene film (with a pore diameter ranging from 300 to 1400 solutions. Mineral scale inhibition efficiency has been tested using PES/
μm) allowed to obtain PEEKWC microcapsules with different 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6] MCs
morphology and diameter varying from 650 to 2200 μm [76]. at lab-scale [17,84]. It has been observed that [BMIM][PF6] loaded in
The coupling of emulsion with the phase inversion technique used MCs interact with oilfield brine solution without losing active ingre­
for the preparation of catalytic PVDF MCs was proposed by Buonomenna dient. The main advantages of PES/[BMIM][PF6] MCs were to eliminate
et al. [77]. Practically, the polymeric drop was formed in the air using loss and easy recovery of the crystal formed at the MCs surface. Simi­
syringe passes through an oil phase and then enters in a coagulation larly, different imidazolium, pyridinium, phosphonium based ILs were
bath. Instantaneously, it allowed the obtention of MCs with diameters loaded on different polymers such as, PES, PSF, PEEKWC based on the
between 600 and 1200 μm. Catalyst ammonium molybdate tetrahydrate phase-inversion process [85]. This investigation declared that polymer
was loaded (ca. 20 wt%) into PVDF MCs and later tested for benzyl solution viscosity influenced directly on the MCs morphology. For
alcohol oxidation to benzaldehyde under solvent-free conditions. example. Higher concentrations of [BMIM][PF6] additive increased the
Importantly, the effect of reaction temperature, substrate, oxidant ratio, viscosity of casting solution reducing the solvent exchange speed. This,
swelling of polymeric MCs during the catalytic process was also further it produced to alter the membrane morphology from a channelled
investigated [78].The highlights of the PVDF catalytic MCs were con­ structures (finger-like) to a spongy type [85]. Similarly amine func­
version efficiency and reusability as a catalyst, which minimized the tionalized imidazolium cation and common anion bis-
product purification process. Capsules’ diameter played a key role in the trifluoromethylsulfonylamide ([TF2N]− ) ionic liquid loaded PES MCs
conversion of aromatic primary alcohol having an average diameter > are evaluated for CO2 permeation from feed composition of 20% CO2,
900 μm. Such a characteristic slightly decreased aldehyde formation due 20% CH4 and 60% N2 by weight. Among the tested ILs, [DEAEBIM]
to restricted diffusion. Similarly, PEEKWC/catalyst MCs (diameter ~ showed maximum CO2 permeation encourage future exploration. Based
1.2 mm) were also synthesized and tested for selective oxidation of on the available literature confirms, by loading suitable components,
benzyl alcohol to aldehyde [79]. The mapping (using EDX technique) of polymer MCs may be vital element in controlling pollutants in various
the PEEKWC catalytic MCs demonstrated a uniform catalyst distribution physical states.
on the shell, inner core and entrapment of catalyst inside the polymeric
matrix. Main parameters (such as polymer concentration, solvent/non- 4.1. MCs characterization techniques
solvent system, additives in coagulation bath) influenced the tailor-
made process morphology similar to membrane (PEEKWC) prepara­ Polymer microspheres are analysed in detail by qualitative and
tion. However, the choice of an oil phase was identified as critical since quantitative tools, i.e. size, shape, morphology (surface and cross-
it involved in sphere formation and should be immiscible with phase 2. section), porosity, stability (mechanical, thermal), swelling (hydro­
To achieve a satisfactory formulation of phase 3, both pure water and philic and hydrophobic solvents) and chemical composition. Maiden
water: alcohol mixture was tested. Alcohols were mixed with water to analysis involves with MCs size and shape through digital and scanning
reduce the surface tension of phase 3 and minimize the resistance at the electron microscope images. Qualitative characterization of chemical
interface 2–3. Alcohols with longer chain lengths could not be employed functional groups performed by non-destructive ATR-IR, especially
since they easily mix with phase 2, therefore, smaller chain length al­ when additives/extractant (encapsulated) presence was confirmed this
cohols (e.g., methanol, ethanol and isopropanol) were employed. way. Nature of the MCs which is crucial for stability and application
Several research reports describe adsorption as an efficient way to investigated via swelling technique and solvent/water holding capacity.
control Arsenic (As) pollution since it requires simple cost-effective Thermal characteristics identified by using thermo gravimetric analysis
operation/adsorbents. MCs loaded with titanium oxide (TiO2) on (TGA) and differential scanning calorimetry (DSC) reveals composite
different polymer matrix (including PES, PEEKWC, and chitosan) were nature (physical and chemical compatibility) of MCs. TGA also provide
fabricated by an amalgamation of PI and pressure extrusion techniques. indirect confirmation of encapsulated materials quantitative values
The size and morphology of TiO2 loaded MCs were adjusted by changing (loading capacity) and mechanical stability (loss, storage modulus)
internal parameters of the coagulation bath and pore-diameter of analysed by differential mechanical analysis (DMA). Swelling a physical
monoporous polypropylene film employed and evaluated as an Arsenic property decides MCs stability on different solvents (water, alcohol (C1-
adsorbent [80,81]. Gujar et al. [82,83] demonstrated the ability of MCs C5 carbon), volatile hydrocarbon solvents, etc.) and these data support
as chelating agents for radioactive actinide effluent treatment. At this viable future applications (organic or inorganic effluent treatment).
point, the MCs were based on commercial hydrophobic composites Porosity and surface area derived from BET analysis results. MCs
(such as PEEKWC/Cyanex 923, PES/TODGA). Especially, PES/TODGA fabricated by PI method dissected by conventional analytical tools to
beads (diameter between 1.3 and 2 mm) were able to sequestrate spe­ identify application area (pollution control) and efficiency (removal/
cific actinide ions (such as Am3+, UO2+ 4+ 4+
2 , Pu , Np ) and fission product separation capacity). Apart from conventional analytical tools, repro­
3+ 2+
ions (such as Eu and Sr ) [83]. While PEEKWC/Cyanex 923 com­ ducibility (size, shape) and bulk production capacity decides the
posite beads (bead size: 900 μm) containing only 5 wt% Cyanex 923 commercialization of MCs.
displayed a metal sorption capacity towards for uranium (i.e. U(VI)) of
about 38.8 ± 1.9 mg per g of bead [82]. 4.2. Environmental pollution control applications
In principle, it is well documented that the decrease of MCs size may
increase the surface area for an efficient quantitative loading and sep­ Microspheres explored for pollution control especially separation/
aration applications. MCs size reduction (<100 μm) was achieved by removal of metal ions and organic compounds (major pollutants) from
combining phase-inversion (PI) and membrane emulsification (ME) for various effluents. Effluents treatment not only provide relief to pollution
polyethersulfone (PES) MCs fabrication [61]. Such an approach implied but also generate wealth, possible secondary pollution control and the

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S.L. Duraikkannu et al. Colloid and Interface Science Communications 40 (2021) 100329

adsorption technique is an excellent option [94]. Several natural and minimum energy and time scale. Herein, multiple micro syringes and
synthetic adsorbents explored for effluent treatment process keeping in centrifugal force-based micronozzle systems are in use for based bulk
mind the following parameters; adsorption capacity, active surface area, production [87]. On the other hand, the possible use of eco-design
porous nature, inertness (chemical), easy to recover the adsorbate, strategies for the development of scale-up module architecture may be
reusability and cost. For special consideration of reuse/recovery aspect useful for industrial production and eliminate secondary pollution
of adsorption-based pollution control technique, it is more efficient to (waste generation). Finally, we have identified the future perspectives
use adsorbent in a shape specific material than free flowing form and research gaps in the field, as follows:
(powder). Polymer MCs loaded with different types of carrier/extrac­
tant/chelating agent/pore former/ionic liquids/additives fabricated by • Development of technologies and fabrication protocols with minimal
PI act superior adsorbents than in pristine state. Extractants loaded cost.
adsorbent MCs used in ground water (metal ions, volatile organic car­ • New preparation pathways using less hazardous solvents, and
bon), industrial effluent (metal ions), radioactive effluent (actinides), without developing secondary effluents
gas (CO2) and catalytic conversion reactions (phase transfer catalyst). • Fabrication protocols with controlled structure
Using the above mentioned extracted loaded MCs perform adsorption • Tailoring well defined core-shell and core-shell-core structures
process due to the reuse/recover option, by this way health hazardous • Enhanced microstructures with maximum loading capacity
elements can be adsorbed into a stable matrix and physical/chemical • Uniform/homogenous distribution
forces applied for desorption successfully. Thermal/mechanical/chem­ • Microspheres with reduced (lower than 40 μm)
ical stability of synthetic polymer-based MCs as adsorbents outplays the • More inert polymer matrix structures
conventional hurdles involved as of now with pristine form adsorbents. • Surface or skin layer (like membrane morphology).
Apart from this, by enhancing the extractant loading in to MCs reflect
the adsorption/removal performance. Regarding the application and promising implementation of MCs,
research community has initiated to explore their potential in environ­
5. Concluding remarks and challenges and scale-up views in mental applications, such as photocatalyst for water purification
MCs fabrication [88–90], removal of the dyes [91], selective extractions of analytes from
complex environmental samples [92], among others. Hence, the explo­
This review attained the proposed objective of the compilation of ration of the possible application of MCs in other fields will boost the
MCs fabrication using phase-inversion, highlighting technical and establishment of this new engineered materials together with more
chemical conditions that control their morphology (e.g. shape and size). efficient techniques and protocols for their fabrication.
Phase-inversion has proved to be able in developing different types of
MCs for several post applications. Importantly, the implementation of Declaration of Competing Interest
phase-inversion also allows the incorporation of additional agents (such
as inorganic-nanosized materials). Specific technologies (like membrane The authors declare that they have no conflict of interest.
emulsification) are still under development. Based upon findings of the
studies reviewed, it can be asserted that, though having a few limita­ Acknowledgements
tions, these systems cause fewer polluting emissions and less environ­
mental impacts than conventional technologies. Moreover, thanks to DSL thanks EU-FP7 for awarding Marie Curie International Incoming
their advantages in terms of pollutant removal efficiency, environmental Fellowship. This work has been funded by the European Community’s
sustainability, and economic convenience, these systems have attracted Programme (FP7-PEOPLE-IIF- 2008), Grant Agreement No.237855,
the attention of researchers and scientists worldwide to extend their Project Code ILMC. R. Castro-Muñoz acknowledges the School of Engi­
application in a circular economy perspective. Microsphere fabrication neering and Science and the FEMSA-Biotechnology Center at Tec­
methods have evolved over several decades and yield quality in terms of nológico de Monterrey for their support through the Bioprocess
size, shape (spherical) which is a key factor in application viewpoint. (0020209I13) Focus Group.
However, there are still some challenges, e.g. large-scale (mass) pro­
duction of microspheres with homogenous shape and size. Many of the References
reported fabrication processes involve several stages and it hinders the
[1] R. Castro-Muñoz, K.V. Agrawal, J. Coronas, Ultrathin permselective membranes:
scale-up process due to cost, complexity, and time. In some cases, syn­
the latent way for efficient gas separation, RSC Adv. 10 (2020) 12653–12670.
thetic stages within MC fabrication potentially alter the properties, and [2] B. Seoane, J. Coronas, I. Gascon, M.E. Benavides, O. Karvan, J. Caro, F. Kapteijn,
in turn affect MCs properties. To achieve specific control over the ge­ J. Gascon, Metal–organic framework based mixed matrix membranes: a solution
ometry (including size, shape, yield, and reproducibility) is also a key for highly efficient CO2 capture? Chem. Soc. Rev. 44 (2015) 2421–2454.
[3] R. Castro-Muñoz, M.Z. Ahmad, V. Fíla, Tuning of Nano-based materials for
challenge in mass production. Size-specific MCs loaded with selective embedding into low-permeability polyimides for a featured gas separation, Front.
chelating agents have been proven as a reusable sorbent for metal ion Chem. 7 (2020) 1–14.
from various sources. Keeping in mind the potential application of MCs, [4] M.F. Jimenez-Solomon, Q. Song, K.E. Jelfs, M. Munoz-Ibanez, A.G. Livingston,
Polymer nanofilms with enhanced microporosity by interfacial polymerization,
fabricating at a large scale is a latent current need. Importantly, a lab- Nat. Mater. 15 (2016) 760–767.
scale module for MCs mass production should fulfil the following [5] Y. Zhang, J. Sunarso, S. Liu, R. Wang, Current status and development of
criteria: low investment/operating cost, easy to clean and maintain, membranes for CO2/CH4separation: a review, Int. J. Greenh. Gas Control 12
(2013) 84–107.
mechanical/chemical/thermal stability against polymers, solvents, and [6] Y. Liao, R. Wang, A.G. Fane, Engineering superhydrophobic surface on poly
minimum energy for operation process. The coupling of the different (vinylidene fluoride) nanofiber membranes for direct contact membrane
processes with phase-inversion has also released good insights during distillation, J. Membr. Sci. 440 (2013) 77–87.
[7] S.S. Davis, L. Illum, Microspheres as drug carriers, Horiz. Biochem. Biophys. 9
MCs preparation, e.g. the use of a large scale Teflon rotator to fabricate
(1989) 131–153.
PES, PSF, PEEKWC microspheres loaded with different active agents, [8] R. Patel, M. Patel, J. Kwak, A.K. Iyer, R. Karpoormath, S. Desai, V. Rarh, Polymeric
such as activated carbon, ionic liquids, Cyanex923, TODGA, among microspheres: a delivery system for osteogenic differentiation, Polym. Adv.
Technol. 28 (2017) 1595–1609.
others, for various application with uniform size and shape
[9] S. Kockisch, G.D. Rees, S.A. Young, J. Tsibouklis, J.D. Smart, Polymeric
[33,61,82,83,86]. Teflon rotator works on the phase inversion concept microspheres for drug delivery to the oral cavity: an in vitro evaluation of
and thus produce MCs of membrane-like morphology can be useful mucoadhesive potential, J. Pharm. Sci. 92 (2003) 1614–1623.
biomedical applications, especially drug, microbes loading. Interest­
ingly, bulk production of MCs is feasible with this module with

9
S.L. Duraikkannu et al. Colloid and Interface Science Communications 40 (2021) 100329

[10] H.G. Bungenberg de Jong, H.R. Kruyt, Chemistry. - coacervation (partial miscibility [41] Y. Yang, T. Chung, X. Bai, W.-K. Chan, Effect of preparation conditions on
in colloid systems) (Preliminary Communication), in: Proceedings Royal Acad. Vol morphology and release profiles of biodegradable polymeric microspheres
XXXII, 1929. containing protein fabricated by double-emulsion method, Chem. Eng. Sci. 55
[11] M.A. White, The chemistry behind carbonless copy paper, J. Chem. Educ. 75 (2000) 2223–2236.
(1998) 1119–1120. [42] P. Losi, L. Mancuso, T. Al Kayal, S. Celi, E. Briganti, A. Gualerzi, S. Volpi, G. Cao,
[12] R. Castro-Muñoz, B.E. Barragan-Huerta, J. Yañez-Fernandez, Use of gelatin- G. Soldani, Development of a gelatin-based polyurethane vascular graft by spray,
maltodextrin composite as an encapsulation support for clarified juice from purple phase-inversion technology, Biomed. Mater. 10 (2015) 45014.
cactus pear (Opuntia stricta), LWT Food Sci. Technol. 62 (2015). [43] Y. Sasaki, N. Konishi, M. Kasuya, M. Kohri, T. Taniguchi, K. Kishikawa, Preparation
[13] S.A. Agnihotri, N.N. Mallikarjuna, T.M. Aminabhavi, Recent advances on chitosan- of size-controlled polymer particles by polymerization of O/W emulsion monomer
based micro- and nanoparticles in drug delivery, J. Control. Release 100 (2004) droplets obtained through phase inversion temperature emulsification using
5–28. amphiphilic comb-like block polymers, Colloids Surf. A Physicochem. Eng. Asp.
[14] C. Saénz, S. Tapia, J. Chávez, P. Robert, Microencapsulation by spray drying of 482 (2015) 68–78.
bioactive compounds from cactus pear (Opuntia ficus-indica), Food Chem. 114 [44] E. Kamio, A. Kato, S. Yonemura, T. Ono, H. Yoshizawa, Preparation of
(2009) 616–622. monodisperse crosslinked polymelamine microcapsules by phase separation
[15] F. Russo, R. Castro-Muñoz, F. Galiano, A. Figoli, Unprecedented preparation of method, Colloid Polym. Sci. 286 (2008) 787–793.
porous Matrimid ® 5218 membranes, J. Membr. Sci. 585 (2019) 166–174. [45] F. Qi, J. Wu, D. Hao, T. Yang, Y. Ren, G. Ma, Z. Su, Comparative studies on the
[16] S. Rafiq, Z. Man, S. Maitra, A. Maulud, F. Ahmad, N. Muhammad, Preparation of influences of primary emulsion preparation on properties of uniform-sized
asymmetric polysulfone/polyimide blended membranes for CO2 separation, exenatide-loaded PLGA microspheres, Pharm. Res. 31 (2014) 1566–1574.
Korean J. Chem. Eng. 28 (2011) 2050–2056. [46] F. Galiano, K. Briceño, T. Marino, A. Molino, K.V. Christensen, A. Figoli, Advances
[17] D.S. Lakshmi, B. Senthilmurugan, E. Drioli, A. Figoli, Application of ionic liquid in biopolymer-based membrane preparation and applications, J. Membr. Sci. 564
polymeric microsphere in oil field scale control process, J. Pet. Sci. Eng. 112 (2013) (2018) 562–586.
69–77. [47] R. Castro-Muñoz, J. González-Valdez, New trends in biopolymer-based membranes
[18] L.Y. Wang, G.H. Ma, Z.G. Su, Preparation of uniform sized chitosan microspheres for pervaporation, Molecules 24 (2019) 3584.
by membrane emulsification technique and application as a carrier of protein drug, [48] R. Castro-Muñoz, J. Gonzalez-Valdez, Z. Ahmad, High-performance pervaporation
J. Control. Release 106 (2005) 62–75. chitosan-based membranes: new insights and perspectives, Rev. Chem. Eng. (2020)
[19] G.G. Enriquez, S.A.A. Rizvi, M.J. D’Souza, D.P. Do, Formulation and evaluation of 1–16.
drug-loaded targeted magnetic microspheres for cancer therapy, Int. J. [49] M.A. Cerqueira, M.J. Sousa-Gallagher, I. Macedo, R. Rodriguez-Aguilera, B.W.
Nanomedicine 8 (2013) 1393–1402. S. Souza, J.A. Teixeira, A.A. Vicente, Use of galactomannan edible coating
[20] Y. Lin, Y. Li, C.P. Ooi, 5-fluorouracil encapsulated HA/PLGA composite application and storage temperature for prolonging shelf-life of “regional” cheese,
microspheres for cancer therapy, J. Mater. Sci. Mater. Med. 23 (2012) 2453–2460. J. Food Eng. 97 (2010) 87–94.
[21] D.P. Do, S.B. Pai, S.A.A. Rizvi, M.J. D’Souza, Development of sulforaphane- [50] X. Zhang, M. Wang, C.H. Ji, X.R. Xu, X.H. Ma, Z.L. Xu, Multilayer assembled CS-
encapsulated microspheres for cancer epigenetic therapy, Int. J. Pharm. 386 (2010) PSS/ceramic hollow fiber membranes for pervaporation dehydration, Sep. Purif.
114–121. Technol. 203 (2018) 84–92.
[22] H. Zhang, E. Tumarkin, R. Peerani, Z. Nie, R.M.A. Sullan, G.C. Walker, [51] F.L. Mi, S.S. Shyu, Y.M. Lin, Y.B. Wu, C.K. Peng, Y.H. Tsai, Chitin/PLGA blend
E. Kumacheva, Microfluidic production of biopolymer microcapsules with microspheres as a biodegradable drug delivery system: a new delivery system for
controlled morphology, J. Am. Chem. Soc. 128 (2006) 12205–12210. protein, Biomaterials 24 (2003) 5023–5036.
[23] E. Kumacheva, P. Garstecki, Polymer capsules, in: Microfluidic Reactors for [52] K. Zhao, J. Huang, X. Ying, G. Cheng, Macromolecularly imprinted calcium
Polymer Particles, 2011, pp. 170–191. phosphate/alginate hybrid polymer microspheres with the surface imprinting of
[24] R. Priestley, R. Prud’homme, Polymer Colloids: Formation, Characterization and bovine serum albumin in inverse-phase suspension, J. Appl. Polym. Sci. 109 (2008)
Applications, Reds, First edn., Royal Society of Chemistry, Cambridge UK, 2020. 2687–2693.
[25] E.Y. Astakhov, S.F. Zhironkin, I.M. Kolganov, E.R. Klinshpont, P.G. Tsarin, Study of [53] E. Mascheroni, A. Figoli, A. Musatti, S. Limbo, E. Drioli, R. Suevo, S. Talarico,
the formation of the porous structure of membranes during phase separation of a M. Rollini, An alternative encapsulation approach for production of active
poly(ester sulfone) solution, Polym. Sci. - Ser. A 53 (2011) 613–620. chitosan-propolis beads, Int. J. Food Sci. Technol. 49 (2014) 1401–1407.
[26] C.S. Tsay, A.J. McHugh, The combined effects of evaporation and quench steps on [54] D.P. Go, D.J.E. Harvie, N. Tirtaatmadja, S.L. Gras, A.J. O’Connor, A simple,
asymmetric membrane formation by phase inversion, J. Polym. Sci. Part B Polym. scalable process for the production of porous polymer microspheres by ink-jetting
Phys. 29 (1991) 1261–1270. combined with thermally induced phase separation, Part. Part. Syst. Charact. 31
[27] L. Wang, J. Chen, Y. Hung, N. Shammas, Membrane and Desalination (2014) 685–698.
Technologies, Reds, First edn., Springer, Berlin, Heidelberg, 2011, ISBN [55] M. Elgammal, R. Schneider, M. Gradzielski, Preparation of latex nanoparticles
9781588299406. using nanoemulsions obtained by the phase inversion composition (PIC) method
[28] P. Wang, J. Ma, F. Shi, Y. Ma, Z. Wang, X. Zhao, Behaviors and effects of differing and their application in textile printing, Colloids Surf. A Physicochem. Eng. Asp.
dimensional nanomaterials in water filtration membranes through the classical 470 (2015) 70–79.
phase inversion process: a review, Ind. Eng. Chem. Res. 52 (2013) 10355–10363. [56] W. Feng, Z. Yin, W. Wang, L. Chen, X. Zhou, K. Qiu, J. Zhou, Y. Zhang, C. He,
[29] A. Figoli, T. Marino, S. Simone, E. Di Nicolò, X.M. Li, T. He, S. Tornaghi, E. Drioli, Synthesis and characterization of nanofibrous hollow microspheres with tunable
Towards non-toxic solvents for membrane preparation: a review, Green Chem. 16 size and morphology via thermally induced phase separation technique, RSC Adv.
(2014) 4034–4059. 5 (2015) 61580–61585.
[30] A. Khalid, A. Abdel-Karim, M. Ali Atieh, S. Javed, G. McKay, PEG-CNTs [57] N. Muramatsu, T. Kondo, An approach to prepare microparticles of uniform size,
nanocomposite PSU membranes for wastewater treatment by membrane J. Microencapsul. 12 (1995) 129–136.
bioreactor, Sep. Purif. Technol. 190 (2018) 165–176. [58] K. Shiga, N. Muramatsu, T. Kondo, Preparation of poly(D,L-lactide) and copoly
[31] C.A. Smolders, A.J. Reuvers, R.M. Boom, I.M. Wienk, Microstructures in phase- (lactide-glycolide) microspheres of uniform size, J. Pharm. Pharmacol. 48 (1996)
inversion membranes. Part 1. Formation of macrovoids, J. Membr. Sci. 73 (1992) 891–895.
259–275. [59] S. Freitas, H.P. Merkle, B. Gander, Microencapsulation by solvent extraction/
[32] Y. Cao, B. You, L. Wu, Facile fabrication of hollow polymer microspheres through evaporation: reviewing the state of the art of microsphere preparation process
the phase-inversion method, Langmuir 26 (2010) 6115–6118. technology, J. Control. Release 102 (2005) 313–332.
[33] D. Shanthana Lakshmi, A. Figoli, G. Fiorani, M. Carraro, L. Giorno, E. Drioli, [60] F. Qi, J. Wu, H. Li, G. Ma, Recent research and development of PLGA/PLA
Preparation and characterization of ionic liquid polymer microspheres [PEEKWC/ microspheres/nanoparticles: a review in scientific and industrial aspects, Front.
DMF/CYPHOS IL 101] using the phase-inversion technique, Sep. Purif. Technol. 97 Chem. Sci. Eng. 13 (2019) 14–27.
(2012) 179–185. [61] E. Piacentini, D.S. Lakshmi, A. Figoli, E. Drioli, L. Giorno, Polymeric microspheres
[34] H. Kun Hseih, E.M. Woo, Preparation of crosslinked epoxy microparticles via phase preparation by membrane emulsification-phase separation induced process,
inversion, J. Polym. Sci. Part B Polym. Phys. 34 (1996) 2591–2598. J. Membr. Sci. 448 (2013) 190–197.
[35] C. Torras, Macrocapsules, Reds, in: E. Drioli, L. Giorno (Eds.), Encyclopedia of [62] Q. Wei, W. Wei, R. Tian, L.yan Wang, Z.G. Su, G.H. Ma, Preparation of uniform-
Membranes Vol 48, Springer, Berlin, Heidelberg, 2016. sized PELA microspheres with high encapsulation efficiency of antigen by premix
[36] F. Chen, G.S. Luo, Y.J. Wang, Preparation of polysulfone-coated chitosan beads by membrane emulsification, J. Colloid Interface Sci. 323 (2008) 267–273.
emulsion phase-inversion method, J. Appl. Polym. Sci. 91 (2004) 3542–3548. [63] G. Ma, Microencapsulation of protein drugs for drug delivery: strategy,
[37] M. Liu, F. Hsu, C. Yang, Preparation of polymer microspheres by phase-separation/ preparation, and applications, J. Control. Release 193 (2014) 324–340.
aggregation (PSA) technique for color toner applications, Soc. Imaging Sci. [64] F. Qi, L. Yang, J. Wu, G. Ma, Z. Su, Microcosmic mechanism of dication for
Technol. 503 (2007) 256–259. inhibiting acylation of acidic peptide, Pharm. Res. 32 (2015) 2310–2317.
[38] Y. Zeng, K. Wang, J. Yao, H. Wang, Hollow carbon beads fabricated by phase [65] R. Liu, G. Ma, F.T. Meng, Z.G. Su, Preparation of uniform-sized PLA microcapsules
inversion method for efficient oil sorption, Carbon N. Y. 69 (2014) 25–31. by combining Shirasu porous glass membrane emulsification technique and
[39] L. Li, J. Yao, P. Xiao, J. Shang, Y. Feng, P.A. Webley, H. Wang, One-step fabrication multiple emulsion-solvent evaporation method, J. Control. Release 103 (2005)
of ZIF-8/polymer composite spheres by a phase inversion method for gas 31–43.
adsorption, Colloid Polym. Sci. 291 (2013) 2711–2717. [66] R. Liu, G.H. Ma, Y.H. Wan, Z.G. Su, Influence of process parameters on the size
[40] S.K. Pathak, S.C. Tripathi, K.K. Singh, A.K. Mahtele, M. Kumar, P.M. Gandhi, distribution of PLA microcapsules prepared by combining membrane
Removal of americium from aqueous nitrate solutions by sorption onto PC88A- emulsification technique and double emulsion-solvent evaporation method,
impregnated macroporous polymeric beads, J. Hazard. Mater. 278 (2014) Colloids Surf. B: Biointerfaces 45 (2005) 144–153.
464–473.

10
S.L. Duraikkannu et al. Colloid and Interface Science Communications 40 (2021) 100329

[67] R. Liu, S.S. Huang, Y.H. Wan, G.H. Ma, Z.G. Su, Preparation of insulin-loaded PLA/ [82] R.B. Gujar, D.S. Lakshmi, A. Figoli, P.K. Mohapatra, Polymeric beads containing
PLGA microcapsules by a novel membrane emulsification method and its release in Cyanex 923 for actinide uptake from nitric acid medium: studies with uranium and
vitro, Colloids Surf. B: Biointerfaces 51 (2006) 30–38. plutonium, J. Chromatogr. A 1305 (2013) 48–54.
[68] D.M. Lloyd, I.T. Norton, F. Spyropoulos, Processing effects during rotating [83] R.B. Gujar, P.K. Mohapatra, D.S. Lakshmi, A. Figoli, Composite polymeric beads
membrane emulsification, J. Membr. Sci. 466 (2014) 8–17. containing N, N, N’, N’-tetraoctyldiglycolamide for actinide ion uptake from nitric
[69] Y. Liang, H. Yu, G. Feng, L. Zhuang, W. Xi, M. Ma, J. Chen, N. Gu, Y. Zhang, High- acid feeds: batch uptake, kinetic modelling and column studies, J. Chromatogr. A
performance poly(lactic-co-glycolic acid)-magnetic microspheres prepared by 1422 (2015) 206–212.
rotating membrane emulsification for Transcatheter arterial embolization and [84] A. Figoli, D.S. Lakshmi, E. Piacentini, L. Giorno, E. Drioli, Preparation of novel
magnetic ablation in VX2 liver tumors, ACS Appl. Mater. Interfaces 50 (2017) ionic liquid loaded polymeric microspheres by membrane emulsification process,
43478–43489. Procedia Eng. 44 (2012) 1287–1290.
[70] Z. Li, H. Liu, L. Zeng, H. Liu, S. Yang, Y. Wang, Preparation of high internal water- [85] D.S. Lakshmi, T. Cundari, E. Furia, A. Tagarelli, G. Fiorani, M. Carraro, A. Figoli,
phase double emulsions stabilized by a single anionic surfactant for fabricating Preparation of polymeric membranes and microcapsules using an ionic liquid as
interconnecting porous polymer microspheres, Langmuir 30 (2014) 12154–12163. morphology control additive, Macromol. Symp. 357 (2015) 159–167.
[71] S. Sánchez, E. Fàbregas, H. Iwai, M. Pumera, Phase-inversion method for [86] D.S. Lakshmi, A. Figoli, M.G. Buonomenna, G. Golemme, E. Drioli, Preparation and
incorporation of metal nanoparticles into carbon-nanotube/polymer composites, characterization of porous and nonporous polymeric microspheres by the phase
Small 5 (2009) 795–799. inversion process, Adv. Polym. Technol. 31 (2012) 231–241.
[72] K. Suzuki, K. Nishiyama, E. Takeuchi, S. Shim, S. Satoh, Preparation of polystyrene [87] S.M. Kang, G.W. Lee, Y.S. Huh, Centrifugal force-driven modular micronozzle
nanoparticles including fluorescent and hydrophobic materials by polymerization system: generation of engineered alginate microspheres, Sci. Rep. 9 (2019) 1–10.
at phase inversion temperature, Polym. Adv. Technol. 25 (2014) 1077–1081. [88] Z. Liu, H. Bai, D. Sun, Facile fabrication of hierarchical porous TiO2 hollow
[73] S. Munirasu, S.P. Nunes, Porous asymmetric SiO2-g-PMMA nanoparticles produced microspheres with high photocatalytic activity for water purification, Appl. Catal.
by phase inversion, J. Mater. Sci. 49 (2014) 7399–7407. B Environ. 104 (2011) 234–238.
[74] Z. Chen, H.B. Ma, Preparation of superfine low-melting-point metal particles by [89] R. Castro-Muñoz, G. Boczkaj, E. Gontarek, A. Cassano, V. Fíla, Membrane
phase inversion method, Adv. Mater. Res. 97–101 (2010) 1087–1090. technologies assisting plant-based and agro-food by-products processing: a
[75] A. Figoli, G. De Luca, F. Lamerata, E. Drioli, Preparation and characterisation of comprehensive review, Trends Food Sci. Technol. 95 (2020) 219–232.
novel PEEKWC capsules by phase inversion technique, Desalination 199 (2006) [90] L. Renuka, K.S. Anantharaju, S.C. Sharma, H.P. Nagaswarupa, S.C. Prashantha,
115–117. H. Nagabhushana, Y.S. Vidya, Hollow microspheres mg-doped ZrO2nanoparticles:
[76] A. Figoli, G. De Luca, E. Longavita, E. Drioli, PEEKWC capsules prepared by phase green assisted synthesis and applications in photocatalysis and photoluminescence,
inversion technique: a morphological and dimensional study, Sep. Sci. Technol. 42 J. Alloys Compd. 672 (2016) 609–622.
(2007) 2809–2827. [91] B. Bai, N. Quici, Z. Li, G.L. Puma, Novel one step fabrication of raspberry-like
[77] M.G. Buonomenna, A. Figoli, I. Spezzano, R. Morelli, E. Drioli, Combined emulsion TiO2@yeast hybrid microspheres via electrostatic-interaction-driven self-
and phase inversion techniques for the preparation of catalytic PVDF assembled heterocoagulation for environmental applications, Chem. Eng. J. 170
microcapsules, J. Phys. Chem. B 112 (2008) 11264–11269. (2011) 451–456.
[78] M.G. Buonomenna, A. Figoli, I. Spezzano, M. Davoli, E. Drioli, New PVDF [92] N. Fontanals, P.A.G. Cormack, D.C. Sherrington, Hypercrosslinked polymer
microcapsules for application in catalysis, Appl. Catal. B Environ. 80 (2008) microspheres with weak anion-exchange character. Preparation of the
185–194. microspheres and their applications in pH-tuneable, selective extractions of
[79] M.G. Buonomenna, A. Figoli, I. Spezzano, E. Drioli, PEEKWC microcapsules for analytes from complex environmental samples, J. Chromatogr. A 1215 (2008)
selective oxidation of benzyl alcohols to aldehydes, Catal. Commun. 9 (2008) 21–29.
2209–2212. [93] D.S. Lakshmi, Y.S. Sistila, A. Figoli, A.K. Khanna, Ionic liquid loaded polyether
[80] K. Taleb, J. Markovski, Z. Veličković, J. Rusmirović, M. Rančić, V. Pavlović, sulfone microspheres for CO2 separation, Adsorption 26 (2020) 737–747.
A. Marinković, Arsenic removal by magnetite-loaded amino modified nano/ [94] A. Bueken, N.N. Zyaykina, Adsorbents and Adsorption Processes for Pollution
microcellulose adsorbents: effect of functionalization and media size, Arab. J. Control, Pollution Control Technologies, in: Nath Bhaskar, Georgi
Chem. 12 (2019) 4675–4693. Stefanov Cholakov (Eds.), Encyclopedia of Life Support Systems (EOLSS), II, EOLSS
[81] A. Figoli, J. Hoinkis, A. Criscuoli, C. Franz, M. Rycke, C. Block, S. Deowan, Publications, 2009.
R. Islam, E. Drioli, The removal of arsenic from (ground)-water by adsorbent
loaded in polymeric microspheres, J. Harbin Inst. Technol. 19 (2012) 63–66.

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