Microencapsulation of dichromate and paracetamol with Eudragit Retard polymers using phase separation by nonsolvent addition

A coacervation technique for microencapsulation using Eudragit Retard polymers [poly(methyl methacrylates) substituted by quaternary ammonium groups] as wall material is described, based upon phase separation using a cold chloroform-cyclohexane mixture together with polyisobutylene as a stabilizer. The effect of various parameters on the nature and properties of the microcapsules of potassium dichromate and paracetamol has been studied, in particular the alteration in wall content and structure and release rate of contents. The microcapsules are discrete, their properties are reproducible, and various degrees of sustained release are obtained.     

Temperature and pH-Sensitive Polymers with Hydrophobic Spacers for the Controlled Delivery of Drugs

Summary: Acid methacrylates containing hydrophobic aliphatic and aromatic spacers were used to prepare pH-sensitive ampholytic hydrogels and bidimensional temperature- (T) and pH-sensitive hydrogels. Their swelling behaviour was studied by changing the pH and temperature of buffer solutions. Salicylamide, salicylic acid and green fluorescent protein (GFP) as model drugs were loaded into the gels and their release kinetics studied under simulated gastric and intestinal conditions. T- and pH-sensitive hydrogels containing aliphatic spacers show sustained release of analgesics depending on pH (e.g. 7.4); while longer aliphatic spacers resulted in drug release depending on pH and temperature (T < transition T). GFP was released from temperature- and pH-sensitive ampholytic hydrogels after different lag times depending on hydrogel composition.     

Properties of gastroretentive sustained release tablets prepared by combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets

A novel floating sustained release tablet having a cavity in the center was developed by utilizing the physicochemical properties of L-menthol and the penetration of molten hydrophobic polymer into tablets. A dry-coated tablet containing famotidine as a model drug in outer layer was prepared with a L-menthol core by direct compression. The tablet was placed in an oven at 80°C to remove the L-menthol core from tablet. The resulting tablet was then immersed in the molten hydrophobic polymers at 90°C. The buoyancy and drug release properties of tablets were investigated using United States Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The L-menthol core in tablets disappeared completely through pathways in the outer layer with no drug outflows when placed in an oven for 90 min, resulting in a formation of a hollow tablet. The hollow tablets floated on the dissolution media for a short time and the drug release was rapid due to the disintegration of tablet. When the hollow tablets were immersed in molten hydrophobic polymers for 1 min, the rapid drug release was drastically retarded due to a formation of wax matrices within the shell of tablets and the tablets floated on the media for at least 6 h. When Lubri wax? was used as a polymer, the tablets showed the slowest sustained release. On the other hand, faster sustained release properties were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic nature. The results obtained in this study suggested that the drug release rate from floating tablets could be controlled by both the choice of hydrophobic polymer and the combined use of hydrophobic polymers.     

Polycaprolactone-polymethyl methacrylate electrospun blends for biomedical applications

Electrospinning is one of most versatile process to fabricate porous scaffolds in biomedical field. Synthetic polymers such as polycaprolactone (PCL) and polymethyl methacrylate (PMMA) provide excellent properties for biomedical applications due to their biocompatibility and tunable mechanical properties. PCL-PMMA electrospun blends combine compressive/tensile properties of individual polymers as well as biocompatibility/biodegradability. Together with porosity of scaffold, drug/nutrient supply is required in tissue regeneration and healing. High pressure CO₂ has been investigated to plasticize many biopolymers and impregnate drugs in scaffolds. This study explores several compositions of PCL-PMMA electrospun scaffolds for morphological and mechanical properties. These scaffolds are impregnated with hydrophilic (Rhodamine B) and hydrophobic (Fluorescein) dyes using high pressure CO₂ and air plasma treatment. Furthermore, release profiles of dyes have been studied from thin films and porous scaffolds to understand several controlling factors for controlled release applications. Results show dye-polymer interactions, CO₂ impregnation and stress relaxation of electrospun fibers are key factors in release profile from electrospun fibers. This study is a step forward in developing PCL-PMMA based electrospun scaffolds for drug delivery and tissue engineering.     

Stereocontrol in radical polymerization

The stereospecific radical polymerization of vinyl esters, methacrylates, and alpha-substituted acrylates was studied. Fluoroalcohols, as a solvent, have remarkable effects on the stereoregularity of the radical polymerizations of vinyl acetate, vinyl pivalate, and vinyl benzoate, affording polymers rich in syndiotacticity, heterotacticity, and isotacticity, respectively. This method was successfully applied to the polymerization of methacrylates to give syndiotactic polymers. The steric repulsion between the entering monomer and the chain-end monomeric unit bound by the solvent through hydrogen bonding is important for the stereochemical control in these systems. Lewis acid catalysts, such as lanthanide trifluoromethanesulfonates and zinc salts, were also effective for the stereocontrol during the radical polymerization of methyl methacrylate, to reduce the syndiotacticity and alpha-(alkoxymethyl)acrylates to synthesize isotactic and syndiotactic polymers. Radical polymerization of the methacrylates bearing a bulky ester group, such as the triphenylmethyl methacrylate derivatives, gave highly isotactic polymers, as in the case of anionic polymerization. In addition, the control of one-handed helical conformation was attained in the radical polymerization of 1-phenyldibenzosuberyl methacrylate using chiral neomenthanethiol or cobalt(II) complexes as an additive.     

Synthesis of traditional and ionic polymethacrylates by anion catalyzed group transfer polymerization

The hydrophobic ionic liquid 1‐butyl‐1‐methylpyrrolidinium bis(trifluoromethylsulfonyl)imide was successfully used as solvent in group transfer polymerization of traditional methacrylates (methyl methacrylate, n‐butyl methacrylate, and benzyl methacrylate) and of ionic liquid methacrylates (ILMAs). This demonstrates that this ionic liquid makes reaction conditions, which do not require the use of ultra‐dried solvents. The ILMAs were N‐[2‐(methacryloyloxy)ethyl]‐N,N‐dimethyl‐N‐alkylammonium bis(trifluoromethylsulfonyl)imides bearing methyl, ethyl, propyl, butyl, or hexyl substituents. Increasing size of the alkyl substituent at the cation results in decreasing glass transition temperature in case of both ionic liquid methacrylates and polymers derived of them. Furthermore, the glass transition temperature is significantly higher for these polymers compared with the ionic liquid methacrylates, and the effect of glass transition temperature reduction with increasing size of the alkyl substituent is stronger for the polymers. A mechanism was proposed explaining the catalytic function of the ionic liquid used as solvent for polymerization. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2849–2859     

1,3,5,5-tetraphenyl-Δ3-1,2,4-triazolin-2-yl radical–properties in the controlled radical polymerization of poly(methyl methacrylate) and polystyrene

The triazoline derivative 1 was used as an additive in the chain-growth controlled radical polymerization of vinylic monomers to afford narrowly distributed polymers. This new system is applicable to styrene as well as to methacrylates. The monomer consumption and the variation of the molar mass were monitored with time. Thermal properties of the obtained polymers were also studied. After isolation of the polymers, the growth of the chains was re-initiated in the presence of a second monomer and yielded block copolymers.     

Asymmetric polymerization of methacrylates

The syntheses of optically active polymers having helical conformation from bulky methacrylates are reviewed focusing on selected topics. The monomers include triphenylmethyl methacrylate and its analogues. Asymmetric anionic polymerization of the monomers gives isotactic, optically active polymers having a helical structure with excess helicity. The isotactic content and the extent of helical‐sense excess depend on the monomer structure and the reaction conditions. In the case of methacrylates, completely isotactic and single‐handed helical polymers can be produced by asymmetric anionic polymerization (helix‐sense‐selective polymerization). Asymmetric radical polymerization is also possible for this class of monomer. Some of the helical polymers show chiral recognition ability toward a wide range of racemic compounds. Polymers having main‐chain configurational chirality are also discussed.     

Magnetically responsive hydrophobic pockets for on–off drug release

The vast majority of drugs available on the market are hydrophobic compounds. As a result, their poor water solubility can critically compromise the overall absorption of these drugs by patients. Although numerous different strategies have been developed to improve their bioavailability, the controlled delivery of these drugs is still a challenge. In this sense, stimuli-responsive hydrogels could be a solution to improve administration and stable release. However, the strategies required to render hydrogels hydrophobic mostly rely on weak hydrophobic interactions, which can lead to disassembly of the system and undesired burst discharge. Accordingly, the on-demand release of poorly water-soluble drugs is still a major milestone in this field. To circumvent these setbacks, we present for the first time a hydrophobic, magnetically responsive hydrogel based on the diaminotriazine (DAT) skeleton. The versatility of DATs in terms of H-bond formation and metal complexation simultaneously endows the hydrogel with hydrophobicity and magnetic responsiveness, thus allowing both the efficient loading and on–off release of a model hydrophobic drug as well as of a hydrophobic bioactive substance. Theoretical calculations further suggested stable formation of DAT aggregates that operate as efficient hydrophobic cavities or ‘pockets’ for these compounds. Moreover, these materials were found to be suitable for enhancing the viability and growth of cell lines often used as in vitro models of neuronal function and differentiation. The present magnetic hydrogels hold interesting potential for tissue engineering as biocompatible scaffolds for the on-demand release of hydrophobic compounds, which remains the focus of current research efforts.     

Ambient‐temperature copper‐catalyzed atom transfer radical polymerization of methacrylates in ethylene glycol solvents

The use of ethylene glycol solvents in the room‐temperature atom transfer radical polymerization (ATRP) of various hydrophobic and hydrophilic methacrylates is demonstrated. Unlike many of the very polar solvents described in the literature for room‐temperature ATRP, these solvents have good solvency for a wide range of polymers and monomers and are cheap and relatively nontoxic. Ethylene glycols with one hydroxyl and one methoxy group, such as tri(ethylene glycol) monomethyl ether (TEGMME), provide optimal results. The polymerization of methyl methacrylate in TEGMME with CuBr/N,N,N′N′,N″‐pentamethyldiethylenetriamine as the catalyst requires the addition of CuCl₂ at the beginning of the reaction to produce well‐controlled polymerizations. This leads to polymers with predictable molecular weights and relatively narrow polydispersities. Polymerization in solvents that are fully methoxy‐capped terminate prematurely because of catalyst precipitation. The electrochemical behavior of copper complexes in selected solvents is examined to determine why these solvents provide good rates at room temperature. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1588–1598, 2005     

Hyperbranched methacrylates by self-condensing group transfer polymerization

The synthesis of hyperbranched methacrylates was achieved by self-condensing group transfer polymerization of 2-(2-methyl-1-triethylsiloxy-1-propenyloxy)ethyl methacrylate ( 1 ). “Back-biting” is shown to be the predominant side reaction. In spite of this, the compact nature of the hyperbranched molecules was demonstrated through SEC-viscosity measurements and comparison with a linear analogue. The degree of branching can be controlled by copolymerization with conventional monomers, e.g. MMA, and the living polymers can be used as macroinitiators for star-shaped polymers.     

聚丙烯酰胺类疏水缔合物的增黏因素研究

合成了6种不同修饰度的聚丙烯酰胺疏水聚合物(PAM1~PAM6), 考察了聚合度、 共聚物片段含量及疏水基团大小等内部因素和聚合物的抗剪切能力、 剪切恢复性及抗盐性等外部因素对这些疏水聚合物分子间、 分子内缔合的影响规律.     

温度及pH敏感的β-环糊精聚合物微球的合成及药物控制释放研究

以反相乳液聚合得到了β-CD聚合物微球,对β-CD微球进行氯乙酰化改性后,利用原子转移自由基聚合的方法把聚甲基丙烯酸N ,N 二甲氨基乙酯(PDMAEMA)接枝到β-CD微球上,从而得到了具有温度和pH响应性的β- CD聚合物微球.通过红外光谱、元素分析确定了PDMAEMA接枝的β- CD微球的结构,采用热台偏光显微镜直接观测到了β- CD微球的温度和pH敏感性.对模型药物染料木素(GNT)和苯丁酸氮芥(CLB )进行了控制释放研究,结果表明pH值可对微球的“内环境”起到“开 关”作用,从而可构筑出一种新型的药物控制释放体系.     

含树枝体疏水缔合聚合物——聚醚树枝体改性聚丙烯酰胺的合成和性质

疏水缔合聚合物是一类含有少量疏水基团的水溶性功能高分子.在水溶液中,这类聚合物在疏水作用驱动下容易发生缔合,并伴随产生独特的缔合行为和溶液性质,因此研究这类聚合物具有重要的理论和应用意义.     

Carbohydrate polymers as controlled release devices for pesticides

Controlled release technology addresses problems associated with excessive use of toxic agricultural chemicals. This paper reviews the studies on the use of carbohydrate polymers as controlled release matrices for pesticides. Alginates, starch and its derivatives, chitosan, carboxymethylcellulose and ethylcellulose are some of the natural polymers discussed in this review. The advantages and disadvantages of these polymeric systems as well as the factors that affect pesticide release are presented. A discussion on the polymers’ encapsulation efficiency and release profile is also included, which will aid future researchers in identifying the suitable formulation for controlled release of pesticides. Combination of two polymers, incorporation of sorbents into polymer matrices, and modification of polymer systems are some of the strategies also discussed herein. Recent trends in this area of research include nanoformulation, nanoencapsulation, and the development of polymeric systems with dual properties such as controlled release with photo-protective property and the attract-and-kill strategy. Cytotoxicity studies are being conducted to address safety issues of pesticide handlers as well as to determine the toxicity of the formulation to non-target organisms such as the plant itself.     

Radical polymerization of various alkyl methacrylates in liquid crystalline solvents

The polymerization of methacrylates of methyl, ethyl, butyl, hexyl, octyl, dodecyl, and octadecyl alcohols was studied with 2,2′-azobisisobutyronitrile in the smectic, nematic, cholesteric, and isotropic liquid phases at 50–75°C. N-(4-Methoxyphenylmethylene)phenylamine, N-(4-ethoxyphenyl-methylene)-4-butylphenylamine, cholesteryl octadecanoate, and benzene were used as the solvents. The viscosities of the polymers were enhanced in the mesomorphic solvents. The polymer was converted to the corresponding poly(methyl methacrylate) through hydrolysis and esterification. Tacticities of the resultant poly(methyl methacrylates) were determined by nuclear magnetic resonance spectroscopy. The isotacticities of the polymers obtained in the smectic and the nematic phases were basically the same and appeared to be larger than those of the polymers in the cholesteric and isotropic liquid states. The polymerization of the methacrylates of butyl and longer-chain alcohols deviated from Bernoullian statistics and gave polymers more isotactic than those of methyl and ethyl methacrylates.     

Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: synthesis and slow release of its inclusion complex with a model hydrophobic drug

Hydroxypropyl chitosan-graft-carboxymethyl beta-cyclodextrin (HPCH-g-CM beta-CD) was synthesized by grafting CM beta-CD onto HPCH using water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing agent. Due to the presence of hydrophobic beta-CD rings onto the HPCH backbone, this polymer can be used as a matrix for controlled drug release. The adsorption of a hydrophobic model drug, ketoprofen, by HPCH-g-CM beta-CD microparticles (using tripolyphosphate as an ionic crosslinking agent) fitted well in the Langmuir isotherm equation. The drug dissolution profile showed that HPCH-g-CM beta-CD microparticles provided a slower release of the entrapped ketoprofen than chitosan, and the release behavior was influenced by the pH value of the medium. These results suggest that beta-CD grafted with chitosan derivatives may become a potential biodegradable delivery system to control the release of hydrophobic drugs with pH-responsive capability.     

Biomedical application of responsive ‘smart’ electrospun nanofibers in drug delivery system: A minireview

Electrospinning is a versatile method for producing continuous nanofibers. It has since become an easy and cost-effective technique in the manufacturing process and drawn keen interests in most biomedical field applications. Nanofibers have garnered great attention in nanomedicine due to their resemblance with the extracellular matrix (ECM). Like nanoparticles, its unique characteristics of higher surface-to-volume ratio and the tunability of the polymers utilizing nanofiber have increased the efficiency in encapsulation and drug-loading capabilities. Smart or “stimuli-responsive” polymers have shown particular fascination in controlled release, where their ability to react to minor changes in the environment, such as temperature, pH, electric field, light, or magnetic field, distinguishes them as intelligent. Polymers are a popular material for the design of drug delivery carriers; consequently, various types of drugs, including antiviral, proteins, antibiotics, DNA and RNA, are successfully encapsulated in the pH-dependent nanofibers with smart polymers which is a polymer that can respond to change such as pH change, temperature. In this minireview, we discuss applications of smart electrospun pH-responsive nanofibers in the emerging biomedical developments which includes cancer drug targeting, oral controlled release, wound healing and vaginal drug delivery.     

Multistimuli responsive amphiphilic graft poly(ether amine): Synthesis,characterization, and self‐assembly in aqueous solution

We reported that multiresponsive amphiphilic graft poly(ether amine)s (agPEAs) comprised of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic octadecyl alkyl chain as side‐chain were prepared through one‐pot synthesis. In aqueous solution, these obtained agPEAs can self‐assemble into stable nanomicelles, whose aggregation can be controlled by temperature, pH, and ionic strength with tunable cloud point (CP). In the presence of these obtained agPEAs, hydrophobic dye Nile red can be dispersed into aqueous solution and hydrophilic dye methyl orange can be dispersed into nonpolar toluene. The agPEAs are expected to be potential in application such as encapsulation and controlled release of drugs, due to their simple synthesis, amphiphilicity, and multistimuli response. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 327–335, 2010     

Synthesis and characterization of new ointment-like poly(ortho esters)

Ointment-like poly(ortho esters) were synthesized for the first time from the reaction of 3,9-bis(methylene)-2,4,8,10-tetraoxaspiro[5. 5] undecane with poly(ethylene glycol)-400, N,N-bis(2-hydroxyethyl)-n-hexadecylamine and N,N-bis(2-hydroxyethyl) palmitamide, respectively. The obtained polymers were characterized by 1H NMR spectra, 13C NMR spectra, elemental analyses, light scattering, and measurements of intrinsic viscosity. The influence of catalyst on the intrinsic viscosity of polymers was investigated. The 9-[(1,3-dihydroxy-2-propoxy) methyl] guanine controlled release profiles of hydrophobic ointment-like polymers such as polymer P_II in vitro were also discussed.