Synthesis of oily core‐hybrid shell nanocapsules through interfacial free radical copolymerization in miniemulsion: Droplet formation and nucleation

Nanocapsules with an oily core and an organic/inorganic hybrid shell were elaborated by miniemulsion (co)polymerization of styrene, divinylbenzene, γ‐methacryloyloxy propyl trimethoxysilane, and N‐isopropyl acrylamide. The hybrid copolymer shell membrane was formed by polymerization‐induced phase separation at the interface of the oily nanodroplets with water. It was shown that the size, size distribution, and colloidal stability of the miniemulsion droplets were extremely dependent on the nature of the oil phase, the monomer content and the surfactant concentration. The less water‐soluble the hydrocarbon template and the higher the monomer content, the better the droplet stability. The successful formation of nanocapsules with the targeted core‐shell morphology (i.e., a liquid core surrounded by a solid shell) was evidenced by cryogenic transmission electron microscopy. Both nanocapsules and nanoparticles were produced by polymerization of the miniemulsion droplets. The proportion of nanoparticles increased with increasing monomer concentration in the oil phase. These undesirable nanoparticles were presumably formed by homogeneous nucleation as we showed that micellar nucleation could be neglected under our experimental conditions even for high surfactant concentrations. The introduction of γ‐methacryloyloxy propyl trimethoxysilane was considered to be the main reason for homogeneous nucleation. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 593–603, 2010     

One-pot synthesis of PDMAEMA nanocapsules for controlled release of hydrophobic cargo

In this work, poly((N,N-dimethyl amino)ethyl methacrylate) (PDMAEMA) homopolymers are synthesized using RAFT technique, which is then used as stabilizers to prepare miniemulsion droplets in a toluene/hexadecane(HD)/1,2-Bis-(2-iodoethyl)ethane(BIEE)/hydrophobic molecule/water mixture. Upon the reaction between BIEE and the stabilizers of miniemulsion droplets, the polymeric nanocapsules are formed and capable of encapsulating hydrophobic molecule in their oil core in one-step reaction. The release of hydrophobic cargo from the nanocapsules can be controlled by the variation of amount of surfactant (Tween®20) in the release medium and a long duration sustained release was achieved.     

N-异丙基丙烯酰胺对细乳液聚合制备纳米胶囊形态的影响

将N-异丙基丙烯酰胺(NIPAAm)引入小分子烃为模板的苯乙烯细乳液聚合法制备纳米胶囊的体系.水相引发形成的聚异丙基丙烯酰胺(PNIPAAm)低聚物自由基在聚合温度下(大于其最低临界溶解温度)析出并被苯乙烯细乳液液滴吸附,在热力学推动力和静电斥力的共同作用下,PNIPAAm低聚物倾向于分布在液滴和水的界面上,使液滴界面成为主要的聚合场所,单体从液滴内部向界面扩散补充消耗的单体,生成的聚合物在液滴界面上析出,包覆小分子烃液滴,最终得到纳米胶囊.通过透射电镜观察粒子形态和大小;利用接触角测定仪测定了细乳液液滴的表面张力.考察了NIPAAm用量、油溶性单体/小分子烃比例、交联剂用量及乳化剂和引发剂对的种类对胶囊形态的影响.     

Fluorescent Polyurethane Nanocapsules Prepared via Inverse Miniemulsion: Surface Functionalization for Use as Biocarriers

The functionalization of well‐defined PU nanocapsules with an aqueous core prepared by performing a polyaddition at the interface of inverse (water‐in‐oil) miniemulsion droplets is demonstrated. The miniemulsion technique involving the nanoreactor concept allows one to obtain an encapsulation efficiency as high as 90% within the nanocapsules. A pH independent fluorescent dye is used as a model system for the aqueous core. By varying the molar ratio of the diol to the diisocyanate at a fixed surfactant concentration, the shell thickness of the nanocapsules can be finely tuned. The carboxy‐ and amino‐functionalized surface of the nanocapsules can be tailored by an in‐situ carboxymethylation reaction and by physical adsorption of a cationic polyelectrolyte, i.e. PAEMA or PEI. The increased uptake of amino‐functionalized fluorescent nanocapsules by HeLa cells clearly demonstrates the potential of the functionalized nanocapsules to be successfully exploited as biocarriers.

     

The role of surfactant in controlling particle size and stability in the miniemulsion polymerization of polymeric nanocapsules

The influence of surfactant concentration on particle size and stability of nanocapsules with liquid cores, synthesized by an in situ miniemulsion polymerization process, was investigated. Although the role of surfactant in the synthesis of particles in the nanometer range has frequently been documented, the transition to structured particles, which almost consist of a 1:1 weight ratio of encapsulated liquid hydrophobe to polymeric shell, has not received much attention. Capillary hydrodynamic fractionation (CHDF) analyses were used to evaluate particle size. Results were subsequently used to stoichiometrically calculate the area which is occupied per surfactant molecule on the particle surface. These results were compared with “classical” miniemulsion data, i.e. data generated from the synthesis of polymeric latexes in the presence of a hydrophobe, but at a much lower hydrophobe:monomer ratio as was used here. The surface coverage per surfactant molecule could be related to the surface tension of the latex, thus providing a relationship between particle size and stability. CHDF was furthermore used to investigate particle size after grafting of a secondary PMMA shell. Data obtained from CHDF experiments were in all cases confirmed by TEM analysis of the synthesized particles. To conclude, the synthesis of nanocapsules with liquid cores could be successfully scaled-up, with retention of all the characteristics of the final latex.     

Preparation of mesoporous submicrometer silica capsules via an interfacial sol-gel process in inverse miniemulsion

Mesoporous silica capsules with submicrometer sizes were successfully prepared via the interfacial hydrolysis and condensation reactions of tetraethoxysilane (TEOS) in inverse miniemulsion by using hydrophilic liquid droplets as template. The inverse miniemulsions containing pH-controlled hydrophilic droplets were first prepared via sonication by using poly(ethylene-co-butylene)-b-poly(ethylene oxide) (P(E/B)-PEO) or SPAN 80 as surfactant. TEOS was directly introduced to the continuous phase of an inverse miniemulsion. The silica shell was formed by the deposition of silica on the surface of droplets. The formation of capsule morphology was confirmed by transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM). The mesoporous structure was verified by nitrogen sorption measurements. The specific surface area could be tuned by the variation of the amount of cetyltrimethylammonium bromide (CTAB) and TEOS, and the pore size by the amount of CTAB. The influences of synthetic parameters on the particle size and morphology were investigated in terms of the amount of CTAB, pH value in the droplets, TEOS amount, surfactant amount, and type of solvent with low polarity. A formation mechanism of silica capsules was proposed.     

Miniemulsion polymerizations of n-butyl cyanoacrylate via two routes: towards a control of particle degradation

This study aimed at determining the influence of the mechanism of polymerization on the molar mass and degradation of poly(n-butyl cyanoacrylate) (PBCA) nanoparticles obtained by miniemulsion polymerization. Therefore, nanoparticles of poly(n-butyl cyanoacrylate) were synthesized via radical and/or anionic miniemulsion polymerization stabilized by Brij?78, a POE based surfactant. Polymerization conditions had little influence on the final diameter while it severely affected the final molar masses of PBCA. An increase of the temperature and of the pH of the continuous phase led to higher molar masses. A further increase was observed when a radical initiator was added in the monomer. The evolution of the molar mass of the synthesized poly(n-butyl cyanoacrylate) was followed as a function of time at pH 7.4 by Size Exclusion Chromatography. As expected, the degradation kinetics strongly depended on the polymerization mechanism (anionic or radical).     

Silicone nanocapsules templated inside the membranes of catanionic vesicles

A simple and effective way to synthesize hollow silicone resin particles of controlled diameter is presented. The synthesis utilizes catanionic vesicles as templates for the polycondensation/polymerization processes of 1,3,5,7-tetramethylcyclotetrasiloxane (D4H) within their membranes. Two different surfactant systems were used to form the vesicular templates: mixtures of dodecyltrimethylammonium bromide (DTAB) and sodium dodecylbenzenesulfonate (SDBS) in the cationic (the DTAB/SDBS system) or anionic (the SDBS/DTAB system) rich region of the phase diagram. The templates obtained from these surfactant mixtures form spontaneously unilamellar vesicles in aqueous solution. The vesicular templates swell upon addition of D4H, thus increasing their size. The silicone resin was obtained in acid- or base-catalyzed polycondensation and ring-opening polymerization processes of D4H. In the case of the DTAB/SDBS system the formation of a densely cross-linked silicone material with SiO3/2 units allowed the nanocapsules to retain the vesicular shape after removal of the template, whereas in the SDBS/DTAB system, the polymer produces capsules which are too smooth to support surfactant lysis. The morphology of the silicone nanocapsules was analyzed using transmission electron microscopy (TEM) and, in some cases, atomic force microscopy (AFM). TEM and AFM reveal discrete hollow particles with a small amount of linked or aggregated hollow silica shells.     

In vitro release of protein from poly(butylcyanoacrylate) nanocapsules with an aqueous core

Factors influencing the in vitro release of bovine serum albumin (BSA) from poly(butylcyanoacrylate) (PBCA) nanocapsules, such as the pH value, BSA loading, the polymeric nanocapsule walls and protein molecular weight, were investigated in detail. The BSA release rate was affected by the degradation rate of the polymeric wall and protein loading. For low molecular weight proteins, the initial burst release was faster than that of high molecular weigh proteins and got to equilibrium quickly. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis results showed that BSA encapsulated within PBCA nanocapsules did not suffer covalent aggregation or fragmentation during the initial days of in vitro incubation. For nanocapsules prepared by interfacial polymerization in water-in-oil microemulsions, these findings were useful as a foundation for the development of nanocapsules with desired properties.     

Easy method for preparing nanocrystalline CdS hollow spheres using miniemulsion droplets as templates

CdS hollow spheres with well-controlled morphology and uniform size were successfully prepared using a miniemulsion technique, in which miniemulsion droplets of isooctane prepared with dodecylmercaptane as a co-stabilizer were employed as templates. The SH groups of dodecylmercaptane generated S(-) ions under alkaline conditions, and further reacted with Cd(2+) ions to form cadmium thiolate around the droplets. The cadmium thiolate then reacted with S(2-) ions, stemming from Na(2)S9H(2)O, to directly form CdS hollow spheres owing to the evaporation of isooctane during the reaction and/or the subsequent drying process. No additional dissolution, calcination or additional surface modification of the templates was needed. The size of the hollow spheres could be tuned by altering the molar ratio of the anionic and non-ionic surfactants, while their shell thickness could be adjusted by changing the amount of co-stabilizer.     

Preparation, characterization and biocompatibility of poly(ethylene glycol)-poly(n-butyl cyanoacrylate) nanocapsules with oil core via miniemulsion polymerization

A new type of nanocapsules with an oil core, coated by poly(ethylene glycol) (PEG) was designed. The loading efficiency and the biocompatibility of the polymeric nanocapsules were evaluated when it was used as a carrier for hydrophobic agent paclitaxel. The nanocapsules were synthesized through miniemulsion polymerization of butylcyanoacrylate (BCA) with PEG as initiator. The particle size and zeta potential of nanocapsules were influenced by the PEG content in the polymerization system. Fourier transform infrared (FTIR) spectra and ¹H NMR demonstrated the chemical coupling between PEG and poly(butylcyanoacrylate) (PBCA). Thermal characteristics of the copolymer were investigated by differential scanning calorimetry (DSC). The encapsulation efficiency increased concurrently with the increase of the PEG content in the system. The hemolytic assay and the cytotoxicity measurement showed that the PEG coating could significantly reduce the hemolytic potential and cytotoxicity of the nanocapsules. The results showed that the PEG-PBCA nanocapsules could be an effective carrier for hydrophobic agents.     

小分子液滴为模板制备有机-无机杂化纳米微胶囊

通过细乳液聚合,在正辛烷液滴外包覆一层苯乙烯与甲基丙烯酸-3-三甲氧基硅丙酯(MPS)的共聚物,制备了有机-无机杂化纳米微胶囊.通过透射电镜和动态光散射粒径仪观测其形态,用红外光谱表征了其分子结构.讨论了聚合方法对微胶囊制备的影响;通过溶度参数的计算和实验验证,发现配方中单体体积分数需小于36%才能得到微胶囊;通过界面自由能模型的计算和动力学分析,说明了微胶囊形成的热力学原因;发现共聚物中MPS的加入有利于微胶囊的形成,但若MPS的含量过大将会导致胶囊塌陷;最后阐明了这种微胶囊制备过程的机理.     

Antiseptic Nanocapsule Formation via Controlling Polymer Deposition onto Water-in-Oil Miniemulsion Droplets

The stable nanodroplet was prepared by inverse miniemulsion with an aqueous antiseptic solution dispersed in an organic medium of solvent/nonsolvent mixture containing an oil-soluble surfactant and the polymer for shell formation. The change in gradient of the solvent/nonsolvent mixture, obtained by heating at 50 °C, led to the precipitation of the polymer in the organic phase and deposition onto the large interphase of the aqueous miniemulsion droplets. The monodisperse polymer nanocapsule, with the size range of 80–240 nm, dispersed in cyclohexane phase was achieved as a function of surfactant concentration. By variation of polymer content, molecular weight and type, an encapsulation efficiency of 20–100% was obtained as detected by proton-nuclear magnetic resonance spectroscopy measurement. The nanocapsule could be easily transferred into water as continuous phase resulting in aqueous dispersion with nanocapsule containing the antiseptic agent as an aqueous core. The encapsulated amount of the antiseptic agent was evaluated to indicate the durability of the nanocapsule's wall. Additionally, the different types of polymer having glass transition temperature ranging from −60 to 100°C have been successfully used. Currently, the research work on the incorporation of nanocapsules onto natural rubber (NR) latex in order to prepare NR latex glove containing the antiseptic agent nanocapsules is carried out. By using the simple and versatile layer-by-layer (LbL) technique based mainly on an electrostatic interaction between oppositely charged species, the deposition of nanocapsules onto NR latex film has successfully been fulfilled.     

Preparation of microspheres by an emulsification-complexation method

Microspheres were prepared by complexation of a cationic polymer, polyquaternium-24, and an anionic surfactant, sodium lauryl sulfate (SLS). The cationic polymer solution was emulsified in dimethylsiloxane to give water in silicone emulsion (W/Si), and it was used as a template for the formation of microspheres. The emulsion was dispersed into the SLS solution. In this process, two kinds of droplets, silicone dropletes and microspheres composed of the cationic polymer and SLS, were formed, evidenced by X-ray energy dispersive spectra. The mean diameter of the microspheres was reduced from 105.7 to 64.8 mum as the stirring rate for W/Si preparation increased from 300 to 1000 rpm. It is believed that water droplets in W/Si emulsion, when exposed to SLS solution, could be solidified by the complexation of the cationic polymer and the anionic surfactant.     

Block Copolymer Capsules with Structure‐Dependent Release Behavior

Although high‐boiling non‐solvent induced macrophase separation in emulsion droplets has been widely applied for the fabrication of polymeric capsules, precise control of their structures remains a great challenge. Herein, block copolymer capsules with tunable shell structures were fabricated by employing a non‐solvent as a liquid template in emulsion droplets. The properties of the non‐solvents dictate the phase separation sequence in the droplets and the capsule formation mechanism. Two different pathways for capsule formation were observed, and could be applied to predict the shell structure. The structured capsules could be transformed into mesoporous capsules, which demonstrated an intriguing structure‐dependent release behavior. Capsules with spherical shell structures displayed the best permeability, while those with lamellar shell structures showed the slowest release, but with a stepwise profile. After loading with an anticancer drug, different capsules induced different apoptosis ratios in cancer cell studies.     

Polymeric nanocapsules containing an antiseptic agent obtained by controlled nanoprecipitation onto water-in-oil miniemulsion droplets

The modified nanoprecipitation of polymers onto stable nanodroplets has been successfully applied to prepare well-defined nanocapsules whose core is composing of an antiseptic agent, i.e., chlorhexidine digluconate aqueous solution. The stable nanodroplets were obtained by inverse miniemulsions with an aqueous antiseptic solution dispersed in an organic medium of solvent/nonsolvent mixture containing an oil-soluble surfactant and the polymer for the shell formation. The change of gradient of the solvent/nonsolvent mixture of dichloromethane/cyclohexane, obtained by heating at 50 degrees C, led to the precipitation of the polymer in the organic continuous phase and deposition onto the large interface of the aqueous miniemulsion droplets. The monodisperse polymer nanocapsules with the size range of 240-80 nm were achieved as a function of the amount of surfactant. Using various polymer contents, molecular weights and types, an encapsulation efficiency of 20-100% was obtained as detected by proton-nuclear magnetic resonance spectroscopy ((1)H NMR) measurements. The nanocapsules could be easily transferred into water as continuous phase resulting in aqueous dispersions with nanocapsules containing an aqueous core with the antiseptic agent. The encapsulated amount of the antiseptic agent was evaluated to indicate the durability of the nanocapsule's wall. In addition, the use of different types of polymers having glass transition temperatures (T(g)) ranging from 10 to 100 degrees C in this process has been also successful.     

Preparation of protected photoinitiator nanodepots by the miniemulsion process

The solid photoinitiator Lucirin TPO was encapsulated within a polymer shell by using the miniemulsion process. A solution of Lucirin TPO in methyl methacrylate (MMA) or butyl acrylate (BA)/MMA mixture was miniemulsified in water followed by a polymerization process in which phase separation of the Lucirin TPO and the formed polymer led to amorphously solidified Lucirin TPO nanoparticles encapsulated by polymer. These nanocapsules were freeze-dried and could be redispersed in acidic monomers, which are applied in polymeric dental adhesives. It is shown by ¹H nuclear magnetic resonance spectroscopy that the shell separates the Lucirin TPO, which is sensitive to degradation in acidic media, from an ambient acidic monomer phase and protects it from fast decomposition. Investigations of the release kinetics of Lucirin TPO from the nanocapsules reveal that the kinetics are strongly dependent on the composition of the surrounding continuous phase.     

Encapsulation of emulsion droplets by organo-silica shells

Surfactant-stabilized emulsion droplets were used as templates for the synthesis of hollow colloidal particles. Monodisperse silicone oil droplets were prepared by hydrolysis and polymerization of dimethyldiethoxysiloxane monomer, in the presence of surfactant: sodium dodecyl sulphate (SDS, anionic) or Triton X-100 (non-ionic). A sharp decrease in the average droplet radius with increasing surfactant concentration was found, with a linear dependence of the droplet radius on the logarithm of the surfactant concentration. The surfactant-stabilized oil droplets were then encapsulated with a solid shell using tetraethoxysilane, and hollow particles were obtained by exchange of the liquid core. The size and polydispersity of the oil droplets and the thickness of the shell were determined using static light scattering, and hollow particles were characterized by electron microscopy. Details on the composition of the shell material were obtained from energy-dispersive X-ray analysis. In the case of sodium dodecyl sulphate, the resulting shells were relatively thin and rough, while when Triton X-100 was used, smooth shells were obtained which could be varied in thickness from very thick ( approximately 150 nm) to very thin shells ( approximately 17 nm). Finally, hexane droplets were encapsulated using the same procedure, showing that our method can in principle be extended to a wide range of emulsions.     

Effects of surfactant micelles on solubilization and DPPH radical scavenging activity of Rutin

The interaction of the antioxidant Rutin with the radical DPPH (2,2-diphenyl-1-picrylhydrazyl) in presence of cationic (CTAB, TTAB, DTAB), non-ionic (Brij78, Brij58, Brij35), anionic (SDS) and mixed surfactant systems (CTAB-Brij58, DTAB-Brij35, SDS-Brij35) has been followed by spectrophotometric and tensiometric methods to evaluate the DPPH radical scavenging activity (RSA) of Rutin in these model self-assembled structures. The results show that the solubilization capacity of various single surfactant systems for both DPPH as well as Rutin followed the order cationics > non-ionics > anionic. The radical scavenging activity of Rutin in the solubilized form was higher within ionic micelles than in non-ionic micelles. However, the antioxidant exhibited enhanced activity for the radical in mixed cationic-non-ionic micelles compared with any of the single component micelles. In contrast, anionic-non-ionic mixed micelles modulated the activity of Rutin in-between that seen for pure anionic and non-ionic micelles only.     

Fabrication of hollow silica spheres using droplet templates derived from a miniemulsion technique

Hollow silica spheres have been successfully fabricated by means of a miniemulsion technique, in which miniemulsion droplets of tetraethoxysilane (TEOS) and octane were prepared with cetyltrimethylammonium bromide as a surfactant and hexadecane as a costabilizer and used as templates. As the TEOS diffused out from the droplets, it was hydrolyzed and condensed to form a silica shell at the oil/water interface. In this way, hollow silica spheres could be obtained directly since the miniemulsion droplets of octane could be evaporated very easily during the reaction process or the drying process; neither an additional dissolution nor a calcination process or additional surface modification of the templates were needed.