DSpace at VNU: Microencapsulation of Active Ingredients Using PDMS as Shell Material

The core−shell microcapsules were obtained by phase separation between the core component and the PDMS shell components after repartitioning of the common solvent THF between the PDMS/co

Microencapsulation of Active Ingredients Using PDMS as Shell

Material

Roberto F A Teixeira,†,§ Otto van den Berg,†,§ Le-Thu T Nguyen,†,§,∥ Krisztina Fehe ́r,‡

and Filip E Du Prez*,†,§

†Department of Organic and Macromolecular Chemistry, Polymer Chemistry Research Group, and‡Department of Organic and Macromolecular Chemistry, NMR & Structure Analysis Unit Group, Ghent University, Krijgslaan 281 S4bis, 9000 Gent, Belgium

§SIM vzw, Technologiepark 935, B-9052 Zwijnaarde, Belgium

∥Department of Polymer Materials, Faculty of Materials Technology, Ho Chi Minh City University of Technology, Vietnam National University, Ly Thuong Kiet 268, District 10, Ho Chi Minh City, Vietnam

*S Supporting Information

ABSTRACT: We report an efficient and adaptable method

for the microencapsulation of active ingredients by a

polydimethylsiloxane (PDMS) shell material The core−shell

microcapsules were obtained by phase separation between the

core component and the PDMS shell components after

repartitioning of the common solvent THF between the

PDMS/core material phase and the water phase For the shell

components, two commercially available functional PDMS

polymers containing thiol and vinyl side groups were used

Photo-cross-linking in the presence of 2,2-dimethoxy-2-phenylacetophenone (DMPA) by thiol−ene radical addition was used to form a PDMS-thioether cross-linked shell Variation of the PDMS component thiol to ene ratio resulted in different functionalities on the microcapsules surface and in the bulk, which was analyzed by attenuated total-reflection infrared spectroscopy (ATR-IR) and high-resolution magic-angle NMR-spectroscopy (HR-MAS NMR) Organically modified silica particles were mixed into the PDMS shell, resulting in better mechanical properties of the shell and control over the shell permeability, as measured on the one hand by tensile testing of representative PDMS bulk samples of identical composition as the actual shell material and on the other hand by leaching experiments of the core compounds, such as a tetrathiol and the UV-absorber octocrylene, followed by UV−vis

Polydimethylsiloxane (PDMS) materials are the most common

silicon-based organic polymers and have attracted much

attention due to their unusual properties such as water

repellency, high flexibility, low glass transition temperature,

low surface energy, and biocompatibility.1−4 Because of their

excellent properties, such materials are used in a wide range of

applications including medical and pharmaceutical5,6 (e.g.,

contact lenses, parts of medical devices, drug delivery),

cosmetics7 (e.g., present in shampoos), household, food,

lubricating oils, electronics, etc

Organosiloxane materials have also been used in the

synthesis of core−shell particles (microcapsules).5,8

Micro-capsules represent reservoirs where an active ingredient (core)

is surrounded or coated by a polymeric material or continuous

film (shell) ranging in size from a few hundreds of nanometers

to micrometers Microencapsulation provides environmental

protection of the active ingredient and can also provide control

and triggered release of the core Therefore, a vast number of

applications9using microcapsules can be found in the literature,

including cosmetics,10 food,11 and drug delivery,12 or in the

increasing research field of self-healing materials in which damage-induced cracking is the healing trigger.13−15

Different examples of employing silicon-based organic polymers on microcapsules, being present either in the core

or in the shell, have been described.16,17 Vincent and co-workers16 reported the preparation of modified silica-shell/ silicon-oil-core microcapsules The core templates were prepared by soap free condensation polymerization of diethoxydimethylsilane (DEODMS) in water, forming a silicone oil/water emulsion, while the shells were formed through the condensation of tetraethoxysilane (TEOS) and DEODMS onto the silicone oil droplets Wang and collaborators17reported the fabrication of core−shell particles, also containing silicone in the core Poly(N-isopropylacryla-mide)/poly(dimethylsiloxane)-graf t-polyacrylates (PNIPA/ PDMS-g-PAA) core−shell composites in supercritical carbon dioxide were prepared in order to obtain smart microgels with pH-sensitive shells

Received: September 12, 2014 Revised: November 8, 2014

pubs.acs.org/Macromolecules

A | Macromolecules XXXX, XXX, XXX−XXX

(core), with subsequent coating of an amino silane (shell) onto

the surface of the magnetite nanoparticles

In order to improve the polymer shell physical properties, the

use of inorganics such as silicates, zinc oxide particles, titanium,

or magnesium oxide particles into the shell of core−shell

structures have attracted much attention Organosilicates have

been incorporated in core−shell particles; e.g., Vincent et al.25

prepared core−shell particles by precipitation of a thin layer of

silica from a supersaturated sodium silicate solution into

cross-linked polydimethylsiloxane (PDMS) microgel core particles

The continuous growth of the shell and shell thickness was

controlled by the addition of tetraethoxysilane with very

specific ethanol and ammonia concentrations Raston et al.26

showed an efficient method for the encapsulation and

controlled release of nutraceuticals using mesoporous silica as

the shell material Other approaches to produce silica shelled

microcapsules have also being reported, such as Pickering

stabilization, reported by the Armes27,28 and the Bon

group29−31or emulsion templating using tetraethyl orthosilicate

in acidic or basic conditions.32−34

To our knowledge, despite the numerous examples of core−

shell particles using siloxane-based compounds, PDMS has not

being used for the microencapsulation of reactive ingredients,

such as the ones used in self-healing polymer applications.35−39

In thisfield, due to the high reactivity of the core materials, the

type of shell is usually limited to melamine formaldehyde (MF),

urea formaldehyde (UF), or polyurethane (PU) material

Sottos and co-workers36 reported the microencapsulation of

isophorone diisocyanate (IPDI) via the interfacial

polymer-ization of toluene diisocyanate-based urethane prepolymer with

1,4-butanediol in an oil-in-water emulsion obtaining a

polyur-ethane type of shell The same group has also reported a similar

method for the microencapsulation of reactive amines by

interfacial polymerization of an isocyanate and an amine

stabilized by an inverse Pickering emulsion using nanoclay as

stabilizer.37 Another example comes from Zhang and

collaborators,35 who reported the microencapsulation of

polythiol pentaerythritol tetrakis(3-mercaptopropionate) by in

situ polymerization with melamine formaldehyde in the shell

Herein, we present an innovative method for the

micro-encapsulation of hydrophobic active ingredients by a

polydimethylsiloxane (PDMS) shell material, which allows

straightforward functionalization of the microcapsule shell

surfaces, control over the permeability, and physical strength

of the shells Moreover, it is a fast and broadly applicable

method, which allows the encapsulation of reactive chemicals

such as thiols, amines, and isocyanates The PDMS shell is

cured by application of a fast thiol−ene UV-curing reaction of

dimethylsiloxane trimethylsiloxy-terminated copolymer (4 −5 mol % vinylmethylsiloxane, viscosity 800 −1200 cSt) (vinyl PDMS) were purchased from ABCR and used as received Aerosil R 8200 fumed silica was purchased from Evonik.

Synthesis of Microcapsules All microcapsules, with different vinyl PDMS:thiol PDMS ratios and different quantities of hydrophobic silica particles, were synthesized at the same emulsification rate and

UV light exposure time A typical procedure is as follows: to a double-neck round bottom flask (250 mL), PSMA solution (150 mL, 0.15 wt

% solution using sodium carbonate to increase the pH to 7 and subsequently mixing overnight) was added and purged with nitrogen for 1 min The solution was then stirred at 270 rpm with the help of an adapted overhead mechanical agitator (water phase) Separately, 8.05 g

of thiol PDMS, 10.08 g of vinyl PDMS, and 36.00 g of core material (mineral oil, tetrathiol, tetrathiol with compatibilizer, and a mixture of methyl benzoate or octocrylene) were mixed together, and then 30 g

of THF was added in order to obtain a homogeneous solution 121 mg (0.472 mmol or 0.2 mol % of PDMS shell components) of DMPA photoinitiator was then added to the mixture, and this solution was purged with nitrogen over 1 min (oil phase) In the absence of oxygen, the obtained solution was dropwise added to the PSMA solution under agitation Finally, the obtained emulsion was exposed to UV light at an approximate light intensity (365 nm) of 12 mW/cm2 in a Metalight Classic irradiation chamber for 5 min.

Core Content Analysis The core content of all microcapsules was analyzed by Soxhlet extraction using acetone as solvent The core content of the PDMS microcapsules containing tetrathiol in the core was also analyzed by NMR and DSC (see Supporting Information) Scanning Electron Microscope (SEM) SEM images were performed on a TM-3000 Hitachi table top microscope, using Leit adhesive Carbon Tabs 12 mm from Agar Scientific.

HR-MAS NMR After removal of the core content of microcapsules using Soxhlet extraction, the obtained hollow microcapsules were ground and put in a 4 mm rotor (80 μL) Next, solvent (CDCl 3 ) was added to allow the material to swell, which removes most of the dipolar line broadening typically associated with the solid state, while residual line broadening caused by susceptibility differences can be handled by spinning at the magic angle All 1 H NMR spectra were recorded on a Bruker Avance II 700 spectrometer (700.13 MHz) using

a HR-MAS probe equipped with a 1H, 13C, 119Sn and a gradient channel Samples were spun at a rate of 6 kHz To characterize the gels, 1D 1 H spectra were recorded All spectra were measured with an acquisition time of 1.136 s, in which 32 768 fid points were obtained, leading to a spectral width of 20.6 ppm For qualitative analysis, 8 transients were summed up with a recycle delay of 2 s For quantification, 32 scans were used with 30 s recycling delay to guarantee full relaxation of the signal.

Tensile Testing Tensile testing was performed on a Tinius-Olsen H10KT tensile tester equipped with a 100 N load cell, using cylindrical specimen with an e ffective gage length of 25 mm and a diameter of 4.5

mm The tensile tests were run at a speed of 10 mm/min Test specimens were prepared by filling 1 mL polypropylene syringes with photocurable formulation and photocuring them at an approximate

| Macromolecules XXXX, XXX, XXX−XXX B

light intensity (365 nm) of 12 mW/cm 2 in a Metalight Classic

irradiation chamber for 5 min, resulting in reproducible cylindrical

specimens.

UV −Vis A weight amount of microcapsules was placed in a quartz

cuvette containing 2.5 mL of methyl benzoate Under continuous

stirring conditions, the UV−vis spectra were recorded over time using

a Carry 300 Bio UV−vis spectrophotometer from Variant Each

sample was analyzed 3 times, and during the absorbance

measure-ments the microcapsules were floating on top of the cuvette and

therefore not in fluencing the absorbance value.

ATR-FTIR The ATR-FTIR spectra of the microcapsules were

obtained using a PerkinElmer Spectrum 1000 FTIR infrared

spectrometer, using 16 scans per sample.

The synthesis of polydimethylsiloxane (PDMS) shell/oil core

microcapsules is performed by making use of two available

PDMS oligomers with thiol and vinyl side groups In the

presence of a radical photoinitiator

(2,2-dimethoxy-2-phenyl-acetophenone, DMPA) and under UV exposure, a thiol−ene

reaction is initiated and a cross-linked thiol−ene network is

formed (see Figure 1)

The core−shell particle formation is based on phase

separation of the material to be encapsulated and the PDMS

shell material Addition of THF, a common solvent for both the

core material and the PDMS (both vinyl and thiol PDMS), to

the material that is to be dispersed in water allows simultaneous dispersion of both the core-component and the shell material Addition of the surfactant PSMA to the water phase prevents coalescence and the formation of larger size capsules Diffusion

of THF from the still homogeneous dispersed THF/PDMS/ core droplets into the water phase leads to phase separation of the core component and the PDMS shell components, resulting

in core−shell droplets with a liquid (oil) core and a liquid silicone shell The presence of THF is a key issue in this process Indeed, the absence of THF would not allow the formation of homogeneous droplets (once the PDMS and the hydrophobic core are not miscible), resulting in separate droplets of PDMS and oil core By curing the PDMS oligomers under UV light for 5 min, PDMS-shell/oil-core microcapsules are obtained in a straightforward way (see Figure 2) Figure 2C shows a broken PDMS microcapsule with a defined shell consisting of PDMS cross-linked material and an inner core (black color inside), suggesting a core−shell structure This encapsulation method can be successfully applied for hydrophobic compounds that have no affinity for water and are insoluble in PDMS Hydrophobicity of the compound ensures that PDMS will be on the outside of the droplets On the other hand, encapsulation of polar protic components is not possible

In such cases, solid silicone particles are isolated and do not contain any liquid core In all cases, the obtained microcapsules

Figure 1 Reaction scheme for the formation of a PDMS cross-linked shell by thiol −ene chemistry 40

Figure 2 (A) Optical microscope picture (B) SEM picture of PDMS rubber shell microcapsules containing tetrathiol in the core (C) SEM picture

of a broken microcapsule containing tetrathiol in the core.

| Macromolecules XXXX, XXX, XXX−XXX C

mers and ene-functional polymers are commonly not very

efficient.42

Though, in a recent publication we have shown the

feasibility of the reaction between thiol-functionalized

poly-dimethylsiloxane (PDMS), telechelic vinyl-functionalized

PDMS, and a dithiol PDMS chain-extender to efficiently

form gel-like rubbery materials.43

In the present article, we varied the ratio of thiol to vinyl

PDMS to obtain vinyl or thiol functionalities on the

microcapsules shell surface, by making use of an excess of

one of the components Organic silica particles were added to

the shell material in order to achieve better mechanical and

physical properties and consequently to gain control over the

permeability of the shell

The suggested microencapsulation strategy, using phase

separation in combination with PDMS, is applicable to a vast

number of hydrophobic organic materials, even to very reactive

compounds such as the ones normally used in self-healing

applications.35−39,44 For this study, we have encapsulated

mineral oil, a mixture of methyl benzoate with ethylhexyl

2-cyano-3,3-diphenyl acrylate (octocrylene, UV-absorber), and a

reactive self-healing agent (pentaerythritol

tetra(3-mercapto-propionate) (tetrathiol)) with core contents around 40 wt %

Additionally, without optimization and only to demonstrate the

versatility of the present methodology, we encapsulated

hexamethylene diisocyanate isocyanurate trimer (HDI-trimer)

and a bis-primary amine (Priamine 1074 liquid) with core

contents around 10−15 wt % All core contents were measured

by Soxhlet extraction of dried powder samples using acetone as

extraction solvent at 80°C for 2 days In the case of tetrathiol,

NMR analysis of the extracted core was performed, showing the

presence of free active thiol groups, similar to the pure NMR

spectra (see Figure S1) Moreover, a Soxhlet extraction test

after 1 month, performed on microcapsules stored in a closed

vessel at room temperature, only showed a decrease of 5 wt %

in the tetrathiol content

The encapsulation of a polythiol, such as the tetrathiol

compound, is particularly difficult As mentioned in the

Introduction, the only reported encapsulation method for this

compound makes use of a highly cross-linked melamine

formaldehyde type of shell.35,44 Likewise, as mentioned

above, we have been able to successfully encapsulate this

compound, using the present approach at 0.15 wt % of PSMA

content and 2:1 core:shell ratio (see Supporting Information)

Stable microcapsules, dried as a powder and stored for

numerous months, containing up to 30 wt % of pure tetrathiol

were obtained We further improved this microencapsulation

efficiency up to 40 wt % of core content, making use of a

custom-made compatibilizer between the tetrathiol active

details in the Supporting Information) This core modification increased the affinity between the PDMS shell and the core by reducing its surface tension, as determined by the comparison

of the contact angles between a PDMS shellfilm and a droplet

of pure tetrathiol and a PDMS shell film with a modified tetrathiol core droplet The contact angles were 67° and 24°, respectively (mean average values of thefirst 10 s, see Table S1

of Supporting Information), confirming the much better affinity

of the modified tetrathiol core

The stability, strength, functionality, and permeability of microcapsules are important factors that are governing the end use application of the microcapsules In self-healing applica-tions, for example, the microcapsules are required to be robust and stable for long periods of time without any leakage On the other hand, in cosmetics and pharmaceuticals, there is a need for controlled release of the active ingredients over time For such applications, a more permeable shell is required In the present work, as a result of the PDMS nature being cross-linked

to a low extent and having a low Tg, we expected our microcapsules to be less robust than the classical stiff, highly cross-linked melamine formaldehyde and polyurethane-based types of shells.38,39 Nevertheless, the physical strength of our PDMS microcapsule shells can be improved by the addition of hydrophobized silica nanoparticles Tensile testing of repre-sentative PDMS bulk samples of identical composition as the actual shell material, containing 0, 5, 10, 15, 20, and 25 wt % of hydrophobized silica, showed a steady increase of the E-modulus with silica content from 1 MPa for the pure PDMS material to 2.5 MPa for the PDMS material containing 25 wt %

of hydrophobized silica (Figure 4) Addition of more than 25%

of hydrophobized silica resulted in a thixotropic, highly viscous formulation that was impossible to process In relation to the microcapsule diameter, we did not observe a significant variation when silica nanoparticles are used

Besides the use of silica nanoparticles to vary the physical properties of the PDMS shells, it is expected that varying the thiol to vinyl PDMS ratio will also influence the E-modulus of the microcapsule shells as a result of changing cross-link density To find out the maximum E-modulus, we prepared several cross-linkedfilms, varying the thiol and ene molar ratios

Figure 3 Synthesis of compatibilizer for tetrathiol/PDMS; synthesis

of a modified tetrathiol core.

| Macromolecules XXXX, XXX, XXX−XXX D

of the two PDMS shell components The highest E-modulus

was obtained for a thiol to ene molar ratio of approximately 1 as

determined by NMR (Figure 5)

In addition to the improvement of the mechanical properties

of the PDMS shells, the use of silica nanoparticles could also

decrease the transport of species across the shell, depending on

the nature of the core species and the medium To further

investigate how these nanofillers influence the permeability, a

series of microcapsules containing a mixture of methyl benzoate

and octocrylene (Mw: 361.5) in the core were prepared

Octocrylene is a UV-absorber used in sunscreen lotions45while

methyl benzoate was used as a diluting solvent

For measuring the permeability of the PDMS microcapsules,

we immersed them in a UV−vis cuvette, containing 2.5 mL of

methyl benzoate Then, by osmosis, the UV-active octocrylene

should diffuse from the microcapsule core toward the cuvette

with methyl benzoate The increase of absorbance in the

cuvette was measured over time Figure 6 shows the UV−vis

measurement data, from which it can be confirmed that an

increase of the hydrophobized silica nanoparticles content of

the PDMS microcapsule shells slows down the diffusion of

octocrylene

This indicates that the use of silica nanoparticles plays an important role not only in obtaining microcapsules with improved mechanical properties but also in gaining control over the shell permeability We also found out that the release profile of the octocrylene sun protector follows the same path

as the logistic dose response mathematical equation, which is usually referred to the drug delivery dose response of an individual:46,47

+

a b

t c

ABS

1 ( / )d

in which ABS represents the absorbance; a, b, c, and d are constants; and t is time R2values of 0.994, 0.999, and 0.994 were obtained for respectively 0, 5, and 10 wt % of silica nanoparticles into the PDMS shells

Functionalities of Microcapsules Shell Surface It was shown that by varying the ratio of the two PDMS shell components, the elastic modulus of the microcapsules can be modified Additionally, by changing the thiol to ene ratio, it is expected that free thiol or vinyl groups will be present on the surface of the microcapsules when an off-stoichiometic ratio is applied In other words, a straightforward functionalization of the shell surface is possible, and postmodification reactions can

be easily applied, which can have a significant impact on the compatibility with applied surrounding media

To prove this concept, we have encapsulated mineral oil (a nonreactive core component), varying the two PDMS shell components with a molar ratio of thiol to ene of 0.5 and 3, respectively After the microencapsulation, all mineral oil was removed by Soxhlet extraction with acetone and both microcapsules were analyzed by HR-MAS NMR

The obtained spectra, shown in Figure S4 (Supporting Information), clearly evidence the presence of vinyl bonds at 5.85 ppm for the microcapsules with high molar ratios of vinyl PDMS while this is not observed for the microcapsules with high content of thiol PDMS, in full agreement with the experiments Moreover, a closer look at the HR-MAS spectrum

of the sample with excess of thiol groups (between−0.4 and 2.8 ppm) shown in Figure 7 confirms the presence of free thiol groups, comparable to what we recently observed.43 Both α

Figure 4 E-moduli of the PDMS shell material as a function of

hydrophobized silica content The error bars represent the 95%

confidence interval (three replicates).

Figure 5 Normalized NMR integral of the vinyl group signal of thiol−

ene PDMS networks as a function of the molar thiol to ene ratio The

normalization was done with respect to the methyl silyl signal of

PDMS Triangles are the data points.

Figure 6 Overall absorbance measurements as a function of time of PDMS microcapsules containing UV-active octocrylene in the core, immersed in a cuvette under stirring and with methyl benzoate as solvent Three samples were measured, containing 0, 5, and 10 wt % of silica nanoparticles in the PDMS shells.

| Macromolecules XXXX, XXX, XXX−XXX E

methylene-silyl signals (labeled asγ and β′) are present and are

resolved from other signals related to the α thiomethylene

signals (thiol and thioether, labeled as α and α′), the β

thiomethylene (labeled asβ, overlap with the water signal), and

SH signal (overlap with a signal from a minor impurity, most

presumably due to some traces of mineral oil)

Furthermore, the presence of free thiol groups on the surface

of the microcapsules was also confirmed by ATR-FTIR analysis

For that, we have reacted both types of microcapsules with

hexamethylene diisocyanate in the presence of triethylamine,

acting as catalyst48,49and using chloroform as solvent, followed

by water and acetone washing to remove all the unreacted

compounds Taking into account that free thiols can react with

isocyanates in a 1:1 ratio, a diisocyanate such as hexamethylene

diisocyanate can react with the free thiols of the PDMS shell

bearing free isocyanate groups, which can be converted into

urea groups upon their reaction with water in the medium

(during the washing) Additionally, a thioưurethane bond can

be formed from the reaction between the isocyanate and thiol

groups In the case of microcapsules enriched with free vinyl

PDMS-shell/oil-core particles using two PDMS shell compo-nents, one having free thiol side groups and the other having free vinyl side groups, was reported The coreưshell particle synthesis is based on the phase separation of the active oil-core and PDMS-shell components mixed together in THF In the presence of a water containing surfactant, THF diffuses to the water, and phase separation between the PDMS and oil core occurs within a stabilized droplet In the presence of DMPA initiator and UV exposure, a thiolưene cross-linking reaction occurs between the two PDMS oligomers forming a PDMS shell network Within this method, different hydrophobic ingredients were successfully encapsulated, such as mineral oil,

a mixture of methyl benzoate with 2-ethylhexyl 2-cyano-3,3-diphenyl acrylate, and a reactive self-healing agent (tetrathiol)

It was demonstrated that variations of the thiol to ene molar ratios of the PDMS components have an impact on the elastic modulus of the thiolưene networks, where the highest E-modulus was obtained for a thiolưene molar ratio of approximately 1 In addition, the organic silica particles can

be mixed within the PDMS shell network, resulting in better physical properties (higher E-modulus) of the shell and control over the shell permeability

*S Supporting Information

Information of tuning the core:shell ratio and surfactant concentrations; procedure for the synthesis of the “tetrathiol core with compatibilizer”; contact angle measurements; graph

Figure 7 Selected region of a HR-MAS 1 H NMR spectrum of thiol ư

ene PDMS microcapsules, prepared with excess of “thiol PDMS”,

swollen in deuterated chloroform.

Figure 8 Left: microcapsules synthesized with excess of “thiol PDMS” before (black) and after (red) reaction with hexamethylene diisocyanate Right: microcapsules synthesized with excess of “vinyl PDMS” before (black) and after (red) reaction with hexamethylene diisocyanate.

| Macromolecules XXXX, XXX, XXXưXXX F

of permeability of PDMS microcapsules in D2O followed by

NMR; TGA and DSC graphs of microcapsules This material is

available free of charge via the Internet at http://pubs.acs.org

Corresponding Author

*E-mail: filip.duprez@ugent.be (F.E.D.P.)

Notes

The authors declare no competingfinancial interest

The presented research is funded by SIM and IWT through a

SIM ICON project within the SIBO program The authors

thank Prof José C Martins for the help with the HR-MAS

NMR measurements The 700 MHz part of the Interuniversity

NMR Facility was funded by a FFEU-ZWAP grant of the

Flemish government

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