The formation of hydrophobic inorganic nanoparticles in the presence of amphiphilic copolymers

The presented paper describes a novel procedure for the preparation of inorganic nanoparticles and their surface functionalization in situ dedicated to an application in technical polymers. Using an inverse emulsion technique and amphiphilic block or statistical copolymers as stabilizers, a broad variety of nanoparticles such as ZnO, CdS, MgCO₃, Ni, or Cu can be prepared. The amphiphilic polymers serve not only as surface active compounds in the emulsion but also to hydrophobize the inorganic particles as they remain adsorbed on the surface after the precipitation. As a consequence of the high degree of surface coverage by polymer chains, organic solvents are able to redisperse these particles in the aggregate free manner. The utilization of the block copolymers instead of statistical copolymers resulted in the formation of the particles, which were larger in size and possessed a much broader size distribution. The chemical nature of the adsorbed polymer layer on the particle surface is crucial to the preparation of polymer nanocomposites. The primary goal of this contribution is to demonstrate the universality of such a one-pot synthetic procedure, which was found to be relevant for industrial use.     

Physicochemical evaluation of PLA nanoparticles stabilized by water-soluble MPEO-PLA block copolymers

Different water-soluble MPEO-PLA diblock copolymers with various alpha-methoxy-omega-hydroxyl polyethylene (MPEO) and poly(lactic acid) (PLA) block lengths have been synthesized. Their surface-active properties were evidenced by surface tension (water/air) measurements. In each case the surface tension leveled down above a critical polymer concentration, which was attributed to the formation of a dense polymer layer at the liquid-air interface. The applicability of copolymers as emulsion stabilizers in the preparation of PLA nanospheres by an o/w emulsion/evaporation technique was then investigated. Four copolymers presenting sufficient water solubility and good surfactive properties were used to prepare PLA nanospheres with MPEO chains firmly anchored at the particle surface. The effect of polymer concentration in emulsion on particle size and surface coverage was examined. Whatever the copolymer characteristics, it was found that the optimal concentration to obtain a large amount of MPEO at the particle surface was similar (around 2 g/l). The effect of the copolymer composition on MPEO layer characteristics and on colloidal stability was also evaluated. The conformation of MPEO blocks at the PLA particle surface is discussed in relation to the layer thickness and the surface area occupied per molecule.     

Tailoring of the external and internal morphology of poly-3-hydroxy butyrate microparticles

Some microencapsulation procedures such as oil-in-water (o/w) and water-in-oil-in-water (w/o/w) emulsions were selected in an attempt to produce tailored poly-3-hydroxybutyrate (PHB) microparticles. The effects of several processing parameters such as polymer precipitation, surfactant, solvent, stirring and solvent evaporation rates were also considered. As a rule, low stirring rates at 500 rpm yielded particles ranging between 100 to 250 μm and at rates over 8000 rpm, diameters around 5–10 μm. The surfaces of the bigger particles, observed by scanning electron microscopy (SEM), were rough and the smaller ones were even rougher, irregular, cauliflower like. The extraction of the chloroform under low pressure or to the open atmosphere did not produce any appreciable change in the morphology for either type of particle. Transmission electron microscopy (TEM) micrographs suggest that microparticles obtained by o/w emulsions are monolithics but those obtained by w/o/w emulsions are of capsule-like structure. Microencapsulation of a peptide material such as follicle stimulating hormone was carried out with success using a double emulsion technique. This biomaterial, dissolved in the inner aqueous phase, was able to stabilize the primary emulsion without using a surfactant.     

Biocompatible poly(ethylene glycol)‐poly(γ‐cholesterol‐L‐glutamate) copolymers: Synthesis,characterization, and in vitro studies

A novel amphiphilic poly(ethylene glycol)‐block‐poly(γ‐cholesterol‐L ‐glutamate) (mPEG–PCHLG) diblock copolymer has been synthesized. The mPEG–PCHLG copolymer has good biocompatibility and low toxicity. The mPEG–PCHLG copolymers could aggregate into nanoparticles with PCHLG blocks as the hydrophobic core and PEG blocks as the hydrophilic shell through emulsion solvent evaporation method. The copolymers were characterized by nuclear magnetic resonance spectroscopy, mass spectrum, Fourier transform infrared spectroscopy, and gel permeation chromatography. The particle sizes, size distributions, and zeta potentials of nanoparticles can also be determined by dynamic light scattering and transmission electron microscopy. This work provides a new and facile approach to prepare amphiphilic block copolymer nanoparticles with controllable performances. This novel copolymer may have potential applications in drug delivery and bioimaging applications.© 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Surfactive water-soluble copolymers for the preparation of controlled surface nanoparticles by double emulsion/solvent evaporation

We have already shown that polylactide (PLA) nanoparticles covered with a hydrophilic polymeric layer can be prepared by simple emulsion/solvent evaporation by using amphiphilic copolymers as surfactants during the procedure. The external layer is then constituted by the hydrophilic part of the macromolecular surfactant. This kind of nanospheres is useful for the encapsulation of lipohilic molecules. The use of amphiphilic copolymers as surfactants in the preparation of PLA nanospheres with controlled surface properties, was then applied to the double emulsion/solvent evaporation procedure. The aim was to allow the encapsulation of water-soluble bioactive molecules in PLA particles with controlled surface properties. In this paper, we describe the results obtained with three different water-soluble monomethoxypolyethylene oxide (MPEO)-b-PLA diblock copolymers used as surfactants in the preparation of nanoparticles by double emulsion/solvent evaporation. After organic solvent evaporation, the obtained nanospheres were proved to be really covered by a MPEO layer whose characteristics were determined. It was firstly shown that the MPEO-covered particles did not flocculate at 25 degrees C, even in 4 M NaCl while suspensions of bare nanospheres were destabilized for a NaCl concentration as low as 0.04 M. On the other hand, the suspensions of MPEO-covered nanoparticles in 0.3 M Na2SO4 were found to be very sensitive to temperature as they flocculated at a temperature lying between 45 and 55 degrees C depending on the MPEO-b-PLA composition. This property was attributed to the fact that MPEO is a polymer with a low critical solution temperature. The concentration of MPEO at the nanoparticle surface was then calculated for the three kinds of particles, from the initial flocculation temperature, and was found to be comparable to the value determined directly.     

Loading of hydrophobic materials into polymer particles: implications for fluorescent nanosensors and drug delivery

A straightforward method for loading hydrophobic materials into commercially available polymer nano- or microparticles is described. PMMA and PS nano/microparticles were swelled by an organic solvent with an ionic surfactant (SDS) to stabilize the particles in aqueous solution. FITC and Ru(dpp)3Cl2 were loaded into those particles based on the principle of "like dissolves like". Further surface modification of the loaded particles was achieved via layer-by-layer (LbL) self-assembly. Culture of fibroblasts with the dye-doped, coated particles showed that the cells internalized the fluorescent particles with no apparent toxic effects. The findings suggest the facile process could be useful in a wide range of applications for fluorescent micro/nanosensors and drug delivery.     

Osmotically Driven Formation of Double Emulsions Stabilized by Amphiphilic Block Copolymers

Double emulsions are valuable for the formation of multi‐compartmental structures. A variety of pathways to prepare double emulsions have been developed, but high‐throughput routes to droplets of controlled size and architecture remain scarce. A new single‐step process is introduced for preparation of water‐in‐oil‐in‐water double emulsions by a previously unexplained process of self‐emulsification. We show that the origin of this process is the osmotic stress resulting from the presence of salt impurities within the amphiphilic block copolymers used for emulsion stabilization. Further, we utilize osmotically driven emulsification to tailor the structures of multiple emulsions, which upon solvent evaporation can yield multi‐compartmental capsules or hierarchically structured porous films.     

Preparation of Magnetite Nanoparticles Coated with an Amphiphilic Block Copolymer: A Potential Drug Carrier with a Core‐Shell‐Corona Structure for Hydrophobic Drug Delivery

Summary: The synthesis of magnetic magnetite nanoparticles coated with amphiphilic block copolymers of poly(ethyl methacrylate)‐block‐poly(2‐hydroxyethyl methacrylate) for use as new potential carriers for hydrophobic drug delivery is reported. The results show that a new core‐shell‐corona structural material is obtained with a very narrow molecular weight distribution of the hydrophobic segment (PDI = 1.10). UV‐Vis results show that 37% of progesterone is released from the nanoparticles after 22 h, much slower than free release (99% after 14 h), which demonstrates that the presence of the hydrophobic segment can effectively control the release of hydrophobic drugs.

Synthesis of an amphiphilic block polymer poly(ethyl methacrylate)‐block‐poly(2‐hydroxyethyl methacrylate) on magnetite nanoparticles and their use as potential drug carriers     

Amphiphilic Linear-Branched Copolylactides and Disperse Systems on Their Basis

The linear-branched copolylactides containing linear side poly(ethylene oxide) blocks are synthesized and characterized. The critical micelle concentrations and the aggregative stability and the dispersity of oil/water emulsions stabilized by these copolymers are estimated. The polylactide microparticles are obtained by emulsification followed by evaporation of an organic solvent using acetylsalicylic acid as a model drug. The structure of copolylactides strongly affects the properties of the microparticles. On one hand, the presence of large poly(ethylene oxide) blocks in the linear-branched macromolecules leads to the formation of colloidal systems with a higher aggregative stability of emulsions and a lower size of particles, and on the other hand, the microparticles formed from these copolymers possess a lower incorporation efficiency relative to water-soluble low-molecular-mass compounds and the profile of the release of these compounds is nonlinear and contains the region of accelerated release.     

The effect of formulation variables on the characteristics of insulin-loaded poly(lactic-co-glycolic acid) microspheres prepared by a single phase oil in oil solvent evaporation method

Biodegradable polymeric microspheres are ideal vehicles for controlled delivery applications of drugs, peptides and proteins. Amongst them, poly(lactic-co-glycolic acid) (PLGA) has generated enormous interest due to their favorable properties and also has been approved by FDA for drug delivery. Insulin-loaded PLGA microparticles were prepared by our developed single phase oil in oil (o/o) emulsion solvent evaporation technique. Insulin, a model protein, was successfully loaded into microparticles by changing experimental variables such as polymer molecular weight, polymer concentration, surfactant concentration and stirring speed in order to optimize process variables on drug encapsulation efficiency, release rates, size and size distribution. A 2⁴ full factorial design was employed to evaluate systematically the combined effect of variables on responses. Scanning electron microscope (SEM) confirmed spherical shapes, smooth surface morphology and microsphere structure without aggregation. FTIR and DSC results showed drug–polymer interaction. The encapsulation efficiency of insulin was mainly influenced by surfactant concentration. Moreover, polymer concentration and polymer molecular weight affected burst release of drug and size characteristics of microspheres, respectively. It was concluded that using PLGA with higher molecular weight, high surfactant and polymer concentrations led to a more appropriate encapsulation efficiency of insulin with low burst effect and desirable release pattern.     

Surface active properties of polyoxyethylene macromonomers and their role in radical polymerization in disperse systems

Conventional dispersion polymerization and copolymerization of low-molecular weight (conventional) unsaturated monomers allows preparation of monodisperse and micronsize polymer particles. A similar behavior can be found in the surfactant-free dispersion polymerization of non-traditional vinyl monomers, unsaturated macromonomers. The latter systems allow preparation of random, comb-like, star-like and graft copolymers as well. An interesting alternative arises with the use of amphiphilic reactive macromonomers that contain a polymerizable group and aggregate into an organized structure -- a micelle. Under such conditions the high rate of polymerization and ultrafine (microparticles) polymer dispersions are generated. Thus, the surface-active macromonomers promote the formation of micelles and polymer growth within the main reaction loci -- polymer particles. Furthermore, the surface-active compounds can be formed during the copolymerization of hydrophilic macromonomer and hydrophobic low-molecular weight comonomer. The reactive surface-active oligomeric radicals are incorporated into the polymer matrix or the particle surface layer, which prevents them from subsequent migration. Besides, the covalently bound surface-active groups at the particle surface strongly increase the colloidal stability of final polymer dispersion. This article presents a review of the current literature in the field of the surfactant-free dispersion polymerization of the polyoxyethylene unsaturated macromonomers. Besides a short introduction into some kinetic aspects of radical polymerization of traditional monomers in homogeneous and disperse systems, we mainly focus on the organized aggregation of amphiphilic polyoxyethylene macromonomers, the characterization of amphiphilic graft copolymers and their aggregation properties, and radical copolymerization of polyoxyethylene macromonomers. We discuss the birth and growth of chains, the transfer of reaction loci from the continuous phase to polymer particles, the diffusion-controlled termination, association of amphiphilic reaction by-products, the particle growth by agglomeration, the particle nucleation, the deactivation of polymer chain growth and the colloidal stability. Effects of initiator type and concentration, the surface activity of macromonomer, the macromonomer type and concentration, temperature, additives and the type of continuous phase on the kinetics of polymerization, and colloidal parameters of the reaction system are also evaluated. Variation of the polymer coil density, the polymer-polymer interaction, and polymer-solvent interaction with the molecular weight, diluent and method (light scattering, the size exclusion, etc.) are discussed. Polymerization of macromonomers provides regularly branched polymers with varied branching density. Since both the degree of polymerization and the length of branches may be varied, polymeric materials with specific properties can be prepared.     

Surface Reconstruction by a Coassembly Approach

Materials with switchable surfaces, capable of changing surface properties under external stimuli, are playing a pivotal role in many applications, such as tissue engineering, biosensors, and drug/protein delivery. In this research silica particles with patterned and switchable surfaces are fabricated. Surface micelles on silica particles are formed by coassembly of polymer brushes and “free” block copolymer chains in a selective solvent. The cores of the surface micelles are crosslinked by anthracene photodimerization. After quaternization of the coronae, amphiphilic surface micelles are prepared. The surface micelles are able to rearrange in different media. After treatment with an organic solvent, the surfaces of silica particles are occupied by hydrophobic polymer components; in aqueous solution, the positively charged polymer chains are on the surfaces. The switching of the surface micelles results in changes in surface composition and wetting behaviors.     

端氨基聚乙二醇-聚已内酯二嵌段共聚物的合成及其微球表面氨基和形态的调控

生物降解高分子作为一种重要的生物材料已经发展到第3代[1],实际应用的复杂性不仅要求高分子材料本身具有合适的降解性能、热性能、力学性能和加工性能等,而且还要求高分子材料具有能够刺激细胞生长、识别特定细胞等生物活性特征.高分子材料的这些生物活性主要是通过高分子材料     

无规共聚物自组装球形胶束表面亲水性的耗散粒子动力学模拟

建立了含不同亲疏水粒子比的双亲性无规共聚物粗粒化模型. 采用耗散粒子动力学方法模拟了两亲性无规共聚物选择性溶剂自组装球形胶束表面的亲水性能. 模拟结果表明, 无规共聚物在选择性溶剂中自组装得到实心球形胶束, 球形胶束表面的亲水性与聚合物链亲水粒子含量、溶剂的选择性有关. 随着聚合物链所含亲水粒子增加, 球形胶束表面的亲水性增强. 球形胶束表面的亲水性随着疏水粒子与溶剂粒子间的排斥参数增大而增强, 模拟结果与实验结论一致. 该模拟方法给出的胶束微结构信息可以为双亲无规共聚物分子设计及自组装双亲胶束制备提供一定的理论指导.     

Effect of interfacial free energy on the formation of polymer microcapsules by emulsification/freeze-drying

Hollow polymer microparticles with a single opening on the surface were formed by freeze-drying aqueous polymer colloids swollen with solvent. The results show that the particle morphology is due to phase separation in the polymer emulsion droplets upon freezing in liquid nitrogen, and that morphological changes are driven largely by lowering interfacial free energy. The effects of added surfactant, volume fraction of solvent, type of solvent, and processing conditions on the particle morphology were examined and compared to theoretical predictions. The dried hollow particles were resuspended in a dispersing media and exposed to a second swelling solvent to close the surface opening and form microcapsules. The interfacial free energy difference between the inside and outside surfaces is the driving force for closing the hole on the surface. The emulsification/freeze-drying technique can be used to encapsulate hydrophilic additives in the core of the microcapsules, demonstrating the potential of the technique in controlled-release applications.     

The encapsulation of an amphiphile into polystyrene microspheres of narrow size distribution

ABSTRACT: Encapsulation of compounds into nano- or microsized organic particles of narrow size distribution is of increasing importance in fields of advanced imaging and diagnostic techniques and drug delivery systems. The main technology currently used for encapsulation of molecules within uniform template particles while retaining their size distribution is based on particle swelling methodology, involving penetration of emulsion droplets into the particles. The swelling method, however, is efficient for encapsulation only of hydrophobic compounds within hydrophobic template particles. In order to be encapsulated, the molecules must favor the hydrophobic phase of an organic/aqueous biphasic system, which is not easily achieved for molecules of amphiphilic character.The following work overcomes this difficulty by presenting a new method for encapsulation of amphiphilic molecules within uniform hydrophobic particles. We use hydrogen bonding of acid and base, combined with a pseudo salting out effect, for the entrapment of the amphiphile in the organic phase of a biphasic system. Following the entrapment in the organic phase, we demonstrated, using fluorescein and (antibiotic) tetracycline as model molecules, that the swelling method usually used only for hydrophobes can be expanded and applied to amphiphilic molecules.     

Amphiphilic polymeric particles with core–shell nanostructures: emulsion-based syntheses and potential applications

The design and synthesis of amphiphilic nano- to micro-sized polymeric particles with core–shell nanostructures have attracted more and more attention because of their wide applicability in modern material science and their technological importance in the areas of colloid and interface science. Many synthetic strategies have been developed for the preparation of amphiphilic core–shell particles that consist of hydrophobic polymer cores and hydrophilic polymeric shells. In this review, we focus on emulsion-based approaches and properties of particles produced. These methods are: (1) grafting to functionalized particle that produces a corona-like particle, (2) grafting from reactive seed particle that produces a brush-like particle, (3) copolymerization of reactive macro-monomer with hydrophobic monomer that produces a corona-like particle, (4) emulsion polymerization in the presence of block or comb-like copolymer containing controlled free-radical moiety that produces a multi-layered particle, and (5) redox-initiated graft polymerization of vinyl monomer from a water-soluble polymer containing amino groups that produces a hairy-like particle. Potential applications of some of these particles in drug and gene deliveries, enzyme immobilization, colloidal nanocatalyst, chemical sensing, smart coating, and thermal laser imaging will be discussed.     

Drug-loaded and superparamagnetic iron oxide nanoparticle surface-embedded amphiphilic block copolymer micelles for integrated chemotherapeutic drug delivery and MR imaging

We report on the fabrication of organic/inorganic hybrid micelles of amphiphilic block copolymers physically encapsulated with hydrophobic drugs within micellar cores and stably embedded with superparamagnetic iron oxide (SPIO) nanoparticles within hydrophilic coronas, which possess integrated functions of chemotherapeutic drug delivery and magnetic resonance (MR) imaging contrast enhancement. Poly(ε-caprolactone)-b-poly(glycerol monomethacrylate), PCL-b-PGMA, and PCL-b-P(OEGMA-co-FA) amphiphilic block copolymers were synthesized at first by combining ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and post- modification techniques, where OEGMA and FA are oligo(ethylene glycol) monomethyl ether methacrylate and folic acid-bearing moieties, respectively. A model hydrophobic anticancer drug, paclitaxel (PTX), and 4 nm SPIO nanoparticles were then loaded into micellar cores and hydrophilic coronas, respectively, of mixed micelles fabricated from PCL-b-PGMA and PCL-b-P(OEGMA-co-FA) diblock copolymers by taking advantage of the hydrophobicity of micellar cores and strong affinity between 1,2-diol moieties in PGMA and Fe atoms at the surface of SPIO nanoparticles. The controlled and sustained release of PTX from hybrid micelles was achieved, exhibiting a cumulative release of ~61% encapsulated drugs (loading content, 8.5 w/w%) over ~130 h. Compared to that of surfactant-stabilized single SPIO nanoparticles (r(2) = 28.3 s(-1) mM(-1) Fe), the clustering of SPIO nanoparticles within micellar coronas led to considerably enhanced T(2) relaxivity (r(2) = 121.1 s(-1) mM(-1) Fe), suggesting that hybrid micelles can serve as a T(2)-weighted MR imaging contrast enhancer with improved performance. Moreover, preliminary experiments of in vivo MR imaging were also conducted. These results indicate that amphiphilic block copolymer micelles surface embedded with SPIO nanoparticles at the hydrophilic corona can act as a new generation of nanoplatform integrating targeted drug delivery, controlled release, and disease diagnostic functions.     

Reduction and pH dual‐responsive block copolymers containing pendent p‐nitrobenzyl carbamate functionalities: Synthesis and self‐assembly behavior

We report on the preparation of reduction‐responsive amphiphilic block copolymers containing pendent p‐nitrobenzyl carbamate (pNBC)‐caged primary amine moieties by reversible addition–fragmentation chain transfer (RAFT) radical polymerization using a poly(ethylene glycol)‐based macro‐RAFT agent. The block copolymers self‐assembled to form micelles or vesicles in water, depending on the length of hydrophobic block. Triggered by a chemical reductant, sodium dithionite, the pNBC moieties decomposed through a cascade 1,6‐elimination and decarboxylation reactions to liberate primary amine groups of the linkages, resulting in the disruption of the assemblies. The reduction sensitivity of assemblies was affected by the length of hydrophobic block and the structure of amino acid‐derived linkers. Using hydrophobic dye Nile red (NR) as a model drug, the polymeric assemblies were used as nanocarriers to evaluate the potential for drug delivery. The NR‐loaded nanoparticles demonstrated a reduction‐triggered release profile. Moreover, the liberation of amine groups converted the reduction‐responsive polymer into a pH‐sensitive polymer with which an accelerated release of NR was observed by simultaneous application of reduction and pH triggers. It is expected that these reduction‐responsive block copolymers can offer a new platform for intracellular drug delivery. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1333–1343