Chorng-Shyan Chern

Polymer Vesicles Containing Small Vesicles within Interior Aqueous Compartments and pH-Responsive Transmembrane Channels†

Intermolecular packing of amphiphilic block copolymers into vesicles is of particular interest, owing to the fundamental importance of such systems as a new class of polymer assemblies with well-controlled structures and potential biomedical applications. Similar to conventional liposomes, polymer vesicles usually form a continuous bilayer structure primarily consisting of the hydrophobic blocks of copolymers, but they exhibit markedly enhanced stability and feasibility of incorporating functional groups in response to external stimuli. However, the major limitation of polymer vesicles as biofunctional containers arises from the lack of permeation pathway for hydrophilic cargoes owing to the requirement to maintain the architectural integrity. The vesicles obtained from block co-polypeptides are imparted responsive channels upon the pH-induced conformational change of a polypeptide block. Redox control of the permeability of multilayer microcapsules containing poly(ferrocenylsiliane) was reported. Incorporating channelforming proteins into the vesicle membranes while fully retaining the protein functions represents an important paradigm of equipping polymer vesicles with transmembrane channels. Thus, the transport mechanism, being either size-selective or substrate-specific, can be tailored by the pore proteins selected. It is also desirable to have versatile vesicular assemblies that contain small vesicles within the interior aqueous compartments in a manner similar to discrete organelles within eukaryotic cells, which perform diverse functions and are one of the feature differences from prokaryotic counterparts. Unfortunately, such assembly structural control has not yet been achieved. Herein, we show the first example of polymeric multivesicle assemblies similar to the architectural arrangement of eukaryotic cells, in which both the vesicle membranes are equipped with pH-responsive channels permeable for hydrophilic solutes (Scheme 1). Copolymers comprising acrylic acid (AAc) and acrylate of 1,2-distearoyl-rac-glycerol (distearin acrylate, DSA) were obtained from partial transesterification of poly(N-acryloxysuccinimide) (poly(NAS)) with distearin and then thorough hydrolysis of the unreacted NAS to AAc units. Polymer vesicles were prepared by a double emulsion technique in a water/oil/water (w1/o/w2) system, in which the copolymer was dissolved in the organic phase prior to emulsification. The experimental methods are described in detail in the Supporting Information. THF/CH3Cl solutions of varying ratios, depending on the target vesicle size, were employed as the organic phase. Either water or buffers in the pH range of 4.0–5.5 were used as both the inner (w1) and outer (w2) aqueous phases. The vesicles formed upon the evaporation of organic solvents in w1/o/w2 emulsions. However, the copolymers assembled into micelles above pH 5.5 and large precipitates below pH 4.0. The vesicles were obtained mainly from copolymer with an average molecular weight of 2.97 ; 10 gmol 1 and a composition of 9.1 mol% DSA, unless stated otherwise. Figure 1a confirms that the resultant assemblies are unilamellar vesicles. The laser scanning confocal microscopy (LSCM) image of polymer vesicles in aqueous suspensions was revealed by the fluorescence of Nile red associated with the vesicle membranes. The lyophilized vesicles can be observed by scanning electron microscopy (see the Supporting Information). The fact that such polymer colloids maintain their structural integrity when subjected to transition from the aqueous to dried state reflects their robust stability. Transmission electron microscopy (TEM) examination of the sectioned specimens (ca. 60–90nm thickness) of polymer vesicles indicates that the wall thickness was approximately 25 nm (Figure 1b). The vesicle size can be controlled by adjusting either the THF/CH3Cl ratio used during emulsification or the DSA content of copolymers to give vesicles with diameters ranging from 1 to 15 mm. For example, changing the DSA content of copolymers from 9.1 to 13.1 mol% increases the vesicle diameter by 3–4 mm on the average. In contrast, increasing the THF content of the THF/CH3Cl solution from 2 to 20% (v/v) reduces the vesicle size significantly (Figure 2) because of the increased miscibility with water and the resulting decreased interfacial tension of the polymer-containing oil droplets in the aqueous phase. When the ionization of AAc residues increases to some extent with increasing pH value, the vesicles become equipped with transmembrane channels that are permeable for hydrophilic solutes. Figure 3 shows that, while transport of calcein (a water-soluble fluorescence probe) across the membrane was prohibited at pH 5.0, the probe molecules freely diffused into the vesicular aqueous compartment when the external pH value was increased to 8.0. Calcein was then confined within the compartment simply by adjusting the [*] Prof. H.-C. Chiu, Y.-W. Lin, Y.-F. Huang, C.-K. Chuang Department of Chemical Engineering National Chung Hsing University Taichung 402 (Taiwan) Fax: (+886)4-2285-2636 E-mail: hcchiu@dragon.nchu.edu.tw

Principles and applications of emulsion polymerization

Preface. 1. Introduction. 1.1. Free Radical Polymerization. 1.2. Emulsion Polymerization. 1.3. Colloidal Stability. 1.4. Some Performance Properties for Industrial Applications. References. 2. Interfacial Phenomena. 2.1. Thermodynamic Consideration. 2.2. Surfactants. 2.3. Colloidal Stability. 3. Particle Nucleation Mechanisms. 3.1. Micellar Nucleation. 3.2. Homogenous Nucleation. 3.3. Coagulative Nucleation. 3.4. Mixed Mode of Particle Nucleation Mechanisms. 3.5. Surfactant-Free Emulsion Polymerization. 3.6. Experimental Work on Particle Nucleation. 3.7. Nonionic and Mixed Surfactant Systems. References. 4. Emulsion Polymerization Kinetics. 4.1. Emulsion Polymerization Kinetics. 4.2. Absorption of Free Radicals by Latex Particles. 4.3. Desorption of Free Radicals Out of Latex Particles. 4.4. Growth of Latex Particles. 4.5. Polymer Molecular Weight. References. 5. Miniemulsion Polymerization. 5.1. Polymerization in Monomer Droplets. 5.2. Stability of Monomer Emulsions. 5.3. Type of Costabilizers in Miniemulsion Polymerization. 5.4. Miniemulsion Polymerization Mechanisms and Kinetics. 5.5. Versatility of Miniemulsion Polymerization. References. 6. Microemulsion Polymerization. 6.1. Introduction. 6.2. Formation and Microstructure of Microemulsions. 6.3. O/W Microemulsion Polymerization. 6.4. W/O Microemulsion Polymerization. 6.5. Polymerization Continuous or Bicontinuous Phases of Microemulsions. References. 7. Semibatch and Continuous Emulsion Polymerizations. 7.1. Semibatch Emulsion Polymerization. 7.2. Continuous Emulsion Polymerization. 7.3. Development of Commercial Continuous Emulsion Polymerizations Process. References. 8. Emulsion Polymerizations in Nonuniform Latex Particles. 8.1. Origin of Nonuniform Latex Particles. 8.2. Seeded Emulsion Polymerizations. 8.3. Factors Affecting Particle Morphology. 8.4. Morphology Development in Latex Particles. 8.5. Polymerization Kinetics in Nonuniform Latex Particles. 9. Applications of Emulsion Polymers. 9.1. Physical Properties of Emulsion Polymers. 9.2. Rheological Properties of Emulsion Polymers. 9.3. Film Formation of Emulsion Polymers. 9.4. Foaming and Antifoaming Agents. 9.5. Wetting. 9.6. Surface Modifications. 9.7. Stability of Latex Products. Index.

Radical Polymerization in Direct Mini-Emulsion Systems

Polymerization in direct mini-emulsions is a relatively new polymerization technique which allows the preparation of submicron latex particles within the range 100<particle diameter<500 nm. This process involves the generation of a large population of submicron monomer droplets in water (termed the mini-emulsion) by intensive shear force with the aid of an adequate emulsifier and coemulsifier (or hydrophobe). These stable, homogenized monomer droplets have an extremely large surface area and, therefore, can compete effectively with the monomer-swollen micelles, if present, for the oligomeric radicals generated in water. Monomer droplets may thus become the predominant loci for particle nucleation and polymerization. This article presents a review of the current literature in the field of radical polymerization of conventional monomers and surface-active monomers in direct mini-emulsion systems. Besides a short introduction into some kinetic aspects of radical polymerization in direct emulsion, mini-emulsion and micro-emulsion systems, we mainly focus on the particle nucleation mechanisms and the common and different features between the classical emulsion and finer mini-emulsion polymerization systems. The effects of the type and concentration of initiator, emulsifier, coemulsifier (hydrophobe) and monomer are evaluated. The influence of the complex formation, the close-packed structure, etc. within the mini-emulsion droplet surface layer on the colloidal stability, the nature of the surface film, and the radical entry process are summarized and discussed. These results show that the nature of the coemulsifier (hydrophobe), the weight ratio of emulsifier to coemulsifier, the mechanisms of sonification, the stability of monomer droplets, and the presence or absence of free micelles play a decisive role in the polymerization process.

Synthesis and characterization of amphiphilic poly(ethylene glycol) graft copolymers and their potential application as drug carriers

Amphiphilic graft copolymers comprising monomeric units of stearyl methacrylate, methyl acrylate, acrylic acid and poly(ethylene glycol) acrylate were synthesized and their properties in aqueous systems characterized. The structures of these copolymers were analysed by Fourier transform infra-red and nuclear magnetic resonance spectroscopies while their molecular weights were estimated by static light scattering. The study of critical micelle concentrations and micellar sizes indicated that the formation of micelles is primarily determined by the hydrophobic/hydrophilic properties of these copolymers. Encapsulation of pyrene (as a drug model) into the micelles was found to be dependent on their stearyl methacrylate content. These copolymers also exhibited a sustained release pattern for pyrene in aqueous solutions and might indicate their future applications as potential drug delivery systems.

Kinetics of styrene miniemulsion polymerization stabilized by nonionic surfactant/alkyl methacrylate

Abstract The effects of various reaction parameters on the styrene miniemulsion polymerizations stabilized by nonylphenol polyethoxylate with an average of 40 ethylene oxide units per molecule (NP-40) and dodecyl methacrylate (DMA) at 80°C were investigated. These parameters include the concentrations of DMA ([DMA]), NP-40 ([NP-40]), sodium persulfate ([SPS]), and 2,2′-azobisisobutyronitrile ([AIBN]). A water-insoluble dye was also incorporated into the reaction system to gain a better understanding of the related particle nucleation mechanisms. The polymerization rate decreases with increasing [DMA], whereas it increases with increasing [NP-40], [SPS] and [AIBN]. Several competitive events (e.g. coalescence among the monomer droplets, nucleation in the monomer droplets and micelles, formation of particle nuclei in water, and particle growth) occur simultaneously in the course of polymerization. This is due to the fact that the steric stabilization effect provided by NP-40 is greatly reduced at 80°C and the CMC of the miniemulsion is far below the NP-40 concentrations used in this work. Mixed modes of particle nucleation are operative in this reaction system, but monomer droplet nucleation becomes more important by increasing [DMA] or decreasing [NP-40], [SPS] and [AIBN].

Particle nucleation loci in styrene miniemulsion polymerization using alkyl methacrylates as the reactive cosurfactant

A water-insoluble blue dye was used to study the particle nucleation mechanisms involved in the styrene miniemulsion polymerizations stabilized by sodium dodecyl sulfate (SDS) along with a reactive cosurfactant (e.g., dodecyl methacrylate (DMA) or stearyl methacrylate (SMA)). A mass balance was established to determine the number of latex particles originating from the monomer droplets (N d ) and that of primary particles generated in the aqueous phase (N w ). The accuracy of this method relies on producing a stable miniemulsion during the reaction. About 55% of the monomer droplets initially present in the reaction mixture (N m,i ) can be successfully converted into latex particles for the system stabilized by SDS/DMA. The value of N d is much smaller than N w , Homogeneous nucleation plays an important role in the reaction kinetics, but it becomes less significant when the DMA concentration is increased. On the other hand, the value of N m.i is much larger when the more hydrophobic SMA is chosen as the cosurfactant. As a consequence, nucleation of primary particles in the aqueous phase is greatly reduced. Nevertheless, only 49% of the original monomer droplets can be converted into latex particles during polymerization. The value of N w is comparable to that of N d . Thus, the relatively large population of primary particles generated via homogeneous nucleation cannot be neglected for the SMA stabilized system. In addition, increasing the initiator concentration may enhance the degree of homogeneous nucleation during the early stage of polymerization.

Emulsion polymerization of styrene stabilized by mixed anionic and nonionic surfactants

Abstract The mixed SDS/NP-40 (anionic/nonionic) surfactants were used to examine the generality of Smith-Ewart theory which was originally proposed for emulsion polymerization systems containing anionic surfactants. Our results are consistent with Smith-Ewart theory only when the wt% of NP-40 in the surfactant mixture ([NP-40]) is less than 30%. However, the reaction system deviates from Smith-Ewart theory dramatically when [NP-40] is greater than 50%. The steric stabilization effect provided by pure NP-40 is not strong enough to prohibit the interactive particles from flocculating with one another. On the other hand, the mixed surfactant system can greatly improve the latex stability via the synergetic effects provided by both the electrostatic and steric stabilization mechanisms and, thereby, retard the limited flocculation process. The mixed surfactant system SDS/NP-40 ( 20 80 ) is the best, because it results in the best reproducibility of the experiment and the greatest polymerization rate.

Styrene miniemulsion polymerization initiated by 2,2′-azobisisobutyronitrile

The effects of various parameters on the dodecyl methacrylate (DMA) or stearyl methacrylate (SMA) containing styrene miniemulsion polymerizations were investigated. These parameters include the type of initiators [2,2′-azobisisobutyronitrile (AIBN) vs. sodium persulfate (SPS)], the size of the homogenized monomer droplets, the AIBN concentration, and the SDS concentration. A small quantity of a water-insoluble dye was also incorporated into the polymerization system to study the related particle nucleation mechanisms. The oil-soluble AIBN promotes nucleation in the monomer droplets, whereas homogeneous nucleation predominates in the reaction system with the water-soluble SPS. Homogeneous nucleation, however, cannot be ruled out in the DMA or SMA containing polymerizations with AIBN as the sole initiator. Increasing the level of AIBN or SDS enhances formation of particle nuclei via homogeneous nucleation. The reaction kinetics is primarily controlled by the competitive events of monomer droplet nucleation and homogeneous nucleation.

Effects of mixed surfactants on the styrene miniemulsion polymerization in the presence of an alkyl methacrylate

The influence of the mixed surfactants sodium dodecyl sulfate (SDS) and nonylphenol poly-ethoxylate with an average of 40 ethylene oxide units per molecule (NP-40) on the styrene (ST) miniemulsion polymerization in the presence of dodecyl methacrylate (DMA) and stearyl methacrylate (SMA) was investigated. Both Ostwald ripening and creaming could not be neglected for the miniemulsions stabilized by SDS/NP-40 in combination with DMA upon aging at 35°C, whereas no appreciable Ostwald ripening and creaming were detected for the SMA containing miniemulsions. For both the DMA and SMA containing polymerizations at 80°C, the rate of polymerization (R p ) decreases with increasing NP-40 concentration ([NP-40]). Incorporation of a small quantity of the extremely water-insoluble blue dye into the reaction system was applied to probe the particle nucleation loci. For the DMA containing polymerizations with [NP-40] = 0, 1.25, and 2.50 mM and the SMA polymerization with [NP-40] = 0 mM, homogeneous or micellar nucleation can not be ignored. On the other hand, the more hydrophobic SMA in combination with SDS/ NP-40 effectively retards the particle nucleation occurring in the aqueous or micellar phase.

Critical micelle concentration of mixed surfactant SDS/NP(EO)40 and its role in emulsion polymerization

Abstract In emulsion polymerization of styrene, nearly all of the polymer particle nuclei are formed in micelles. Therefore, it is of fundamental importance to understand the relations involved in micelle formation. In this study, the critical micelle concentrations (CMC) of the mixed surfactant, sodium dodecyl sulfate (SDS)/nonylphenol tetracontylethoxylate (NP(EO)40), were determined for various compositions at 25°C and at 80°C by performing the surface tension measurements. The CMC data were well described by the regular solution model for mixed micelles. The system of mixed micelles exhibits a quite non-ideal behavior, especially at lower temperature (25°C). The effect of the mixed surfactant SDS/NP(EO)40 on the formation of latex particles was demonstrated by a series of styrene emulsion polymerization. Adding only a small amount of the anionic surfactant SDS into the polymerization system can dramatically increase the concentration of latex particles and also reduce the particle size of the latex product. Furthermore, emulsion polymerization of styrene stabilized by the mixed surfactant system does not follow the conventional Smith-Ewart theory when the level of NP(EO)40 is relatively high.