Biodegradable Poly(Lactic Acid) and Poly (Lactide-Co-Glycolide) Polymers in Sustained Drug Delivery

Abstract

Poly(lactic acid) [PLA] and its co-polymers with glycolic acid [PLCG] have been known for the past 20 years of its biodegradability and histocompatibility. Their physico-chemical and biological properties have been found suitable, in many instances, for sustaining drug release in vivo and in vitro from days to months. A wide variety of drugs ranging from small molecular weight therapeutic agents to peptide hormones, antibiotics, chemotherapeutic drugs have been studied using these biodegradable polymers. Several parenteral and oral dosage forms have been investigated, which includes microcapsules, implants, pseudolatices, nanoparticles, tablets, films as well as occular devices for local delivery of drug into the eye. An attempt have been taken in this paper to review the prospect of using these biodegradable polymers for long term parenteral drug delivery of different classes of drugs.     

Biodegradable Poly(Lactic Acid) and Poly (Lactide-Co-Glycolide) Polymers in Sustained Drug Delivery

Poly(lactic acid) [PLA] and its co-polymers with glycolic acid [PLCG] have been known for the past 20 years of its biodegradability and histocompatibility. Their physico-chemical and biological properties have been found suitable, in many instances, for sustaining drug release in vivo and in vitro from days to months. A wide variety of drugs ranging from small molecular weight therapeutic agents to peptide hormones, antibiotics, chemotherapeutic drugs have been studied using these biodegradable polymers. Several parenteral and oral dosage forms have been investigated, which includes microcapsules, implants, pseudolatices, nanoparticles, tablets, films as well as occular devices for local delivery of drug into the eye. An attempt have been taken in this paper to review the prospect of using these biodegradable polymers for long term parenteral drug delivery of different classes of drugs.     

Development of an Implantable,Biodegradable, Controlled Drug Delivery System for Local Antibiotic Therapy

Abstract

A novel drug delivery system was developed using a monoglyceride (Glycerol Monostearate) and a water-soluble release rate modifier as the matrix. Cefuroxime sodium (Zinacef®) was chosen as a model drug in this study. Formulations (cylindrical implants 6 × 6 mm) were prepared by a melt-dispersion method. Dissolution studies were performed using USP paddle method. The effect of glycerol, PEG 400 and their combination on drug release profiles was studied. Two assay methods (UV and HPLC) for cefuroxime analysis were compared. Percent recovery from four formulations (A-D) was higher with UV than HPLC assay. While both UV and HPLC assay methods were developed for cefuroxime, only HPLC assay is stability indicating. Glycerol showed higher accelerating effect than PEG 400 on the drug release. All formulations exhibited extended release of cefuroxime. Degradation of cefuroxime occurred mainly during dissolution suggesting drug stability in the formulations.     

Development of Anticandidal Delivery Systems: (II) Mucoadhesive Devices for Prolonged Drug Delivery in the Oral Cavity

Conventional dosage forms designed for drug delivery in the oral cavity suffer from the disadvantage of an initial burst of activity followed by a rapid decrease in concentration to subtherapeutic levels. To counter this effect, two prolonged-release dosage forms were devised for the treatment of oral candidiasis. These devices were to contain the antifungals, chlorhexidine and clotrimazole, for therapy against Candida albicans, and also benzocaine and hydrocortisone to combat the pain and inflammation secondaly to a candidal infection. Release studies demonstrated that only chlorhexidine and clotrimazole could be delivered in a controlled manner from the mucoadhesive patches. On the other hand, release of all four drugs could be controlled from the mucoadhesive tablets, with optimum release of the drugs in 24 hr achieved using sodium carboxymethylcellulose and polyethylene oxide (85:15) combination tablets.     

聚烯丙基氯化铵调控下多孔羟基磷灰石微球的合成及作为药物载体的应用研究

选用聚烯丙基氯化铵(PAH)作为晶体生长调节剂, 在水热条件下成功制备了多孔羟基磷灰石(Hydroxyapatite, HAP)中空微球。详细研究了反应时间和添加剂浓度等因素的影响: 150℃水热反应12 h, 控制PAH 浓度0.3~0.5 g/L, 可合成尺寸均匀、孔径密集的HAP中空微球。微球生长经历早期前驱体微结构、异相成核、相转化等不同阶段, 聚合物在各阶段都起到重要的调节作用。以典型的布洛芬(ibuprofen, IBU)作为模型药物, 研究微球的药物负载和脱附能力。结果显示: 多孔微球具有良好的药物负载和释放能力, 吸附量较好, 可达到413.65 mg/g。且药物具有较好的pH响应释放行为, 可作为pH敏感靶向药物载体应用到生物医学等领域。     

Implantable Controlled Release Drug Delivery Systems: A Review

Abstract

Origins of rate controlled implantable drug delivery dates back to 1964 when silicone implants were used to prolong a drug effect. Despite much activity in the years since 1964, the progress to a safe, effective and acceptable implant system(s) has been slow. The critical factors in implant research which need to be addressed include: erodibility, reproducibility, lack of irritation and carcinogenicity, lack of dose dumping, duration and pulses. While it is possible to surgically implant and remove drug-containing devices or polymeric matrices, the requirement for such intervention could have a significant negative impact on the acceptability of a product candidate. In recent years, two implant systems have been approved for human use; (a) a silicone-based device (Norplant^R), and (b) a system based on lactide/glycolide copolymers to release a luteinizing hormone - releasing hormone (LHRH) agonist for treatment of male reproductive tract tumours. This approach to drug delivery is very appealing for a number of classes of drugs, particularly those that cannot be given via the oral route, and drug candidates whose therapeutic index is relatively large. This article reviews the background to implantable drug delivery systems, the rationale behind using implantable drug delivery systems, the types of systems being currently researched, and the various methods available for their evaluation.     

Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow‐Focusing Device for Controlled Drug Delivery

Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several therapies approved by the US Food and Drug Administration. Conventional emulsion‐based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug‐loaded microparticles from biodegradable polymers using the microfluidic flow‐focusing (FF) devices and the drug‐delivery properties of those particles. Particles are engineered with defined sizes, ranging from 10 µm to 50 µm. These particles are nearly monodisperse (polydispersity index = 3.9%). A model amphiphilic drug (bupivacaine) is incorporated within the biodegradable matrix of the particles. Kinetic analysis shows that the release of the drug from these monodisperse particles is slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibit a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release is attributed to the uniform distribution of the drug inside the particles generated using the microfluidic methods. These results demonstrate the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs.     

In Vivo Characteristics of Injectable Poly(DL-Lactic Acid) Microspheres for Long-Acting Drug Delivery

Abstract

Poly(DL-lactic acid) (PLA) microspheres containing testosterone (T) were prepared by the solvent evaporation process to evaluate their physical properties such as size distribution, shape, drug content, in vivo controlled drug release, pharmacological influences on the prostate gland in castrated rats, and histopathological findings of tissues surrounding the implants. The in vivo release of T from PLA microspheres containing 30 mg of drug obtained with chloroform was continued over a 6-week period. This effect is attributed to high dispersibility ofT in the device when obtained with chloroform. Both serum drug levels and prostate gland weight recovery suggested the effects of a long-acting drug delivery system. The histopathological findings showed that the devices used were completely degraded 10 weeks after injection.     

新型聚羧酸对苯撑乙炔酯的合成

报道了新型可溶性聚羧酸对苯撑乙炔酯的合成方法。它是以苯乙酸为起始原料 ,首先经过Friedel Crafts反应 ,制备聚苯乙酰高分子 ;后者与几种羧酸酰氯的酯化反应而制得。经IR、H NMR、UV Vis等分析方法对其结构进行了表征。分析数据表明聚羧酸对苯撑乙炔酯具有PPV链状π 共轭结构特征 ,在二甲苯、THF、DMSO等有机溶剂中 ,有较高的溶解性。     

生物降解材料聚乳酸的共聚改性研究进展

概述了生物降解材料聚乳酸的物理机械性能和生物性能,指出对聚乳酸进行改性的必要性及常用方法,其中共聚改性方法是最有效的途径之一.综述了聚乳酸与聚乙醇酸、聚己内酯、聚乙二醇、聚氨基酸等的共聚方法、共聚物的性能及其应用.经共聚改性后聚乳酸的力学性能、亲水性能或反应功能性能可以得到改善,降解周期可实现调控,从而满足在生物医学及环保方面的应用需求.     

Transdermal Delivery Devices: Fabrication,Mechanics and Drug Release from Silk

Microneedles are a relatively simple, minimally invasive and painless approach to deliver drugs across the skin. However, there remain limitations with this approach because of the materials most commonly utilized for such systems. Silk protein, with tunable and biocompatibility properties, is a useful biomaterial to overcome the current limitations with microneedles. Silk devices preserve drug activity, offer superior mechanical properties and biocompatibility, can be tuned for biodegradability, and can be processed under aqueous, benign conditions. In the present work, the fabrication of dense microneedle arrays from silk with different drug release kinetics is reported. The mechanical properties of the microneedle patches are tuned by post‐fabrication treatments or by loading the needles with silk microparticles, to increase capacity and mechanical strength. Drug release is further enhanced by the encapsulation of the drugs in the silk matrix and coating with a thin dissolvable drug layer. The microneedles are used on human cadaver skin and drugs are delivered successfully. The various attributes demonstrated suggest that silk‐based microneedle devices can provide significant benefit as a platform material for transdermal drug delivery.     

聚乳酸多孔微球的制备及释药性能

将聚乳酸(PLLA)/四氢呋喃(THF)溶液分散在甘油(连续相)中,通过自乳化结合热致相分离(TIPS)制备一系列PLLA多孔微球,微球由捆束状纳米纤维组成。通过改变PLLA浓度、(PLLA/THF)∶甘油比值、溶剂种类以及淬火温度等条件研究所得多孔微球结构与形貌。结果表明,PLLA的质量分数为2%~5%、m(PLLA/THF)∶m(甘油)=1∶3、-20℃和-196℃淬火均能得到形状规整的PLLA多孔微球。多孔微球孔隙率和比表面积最高可达95.44%和32.53m2/g。PLLA多孔微球对牛血清蛋白的药载量为0.355 mg/mg,30 h内释放率达到59.8%,是一种非常良好的药物缓释载体。     

生物降解型聚碳酸顺丁烯二酸亚乙酯 1、合成和表征

用CO_2、环氧乙烷、顺丁烯二酸酐进行三元共聚首次得到聚碳酸顺丁烯二酸亚乙酯(PECM),并用IR、~1H NMR、DSC等进行了表征,共聚物链中CO_2和MA单元随机分布,不饱和单元可在0～0.5mol分数之间调节。共聚过程不发生双键交联和构型转化。环氧乙烷的转化率可高达到93％。控制PECM链上的双键含量并使之发生自由基加成反应,得到对热较稳定的可溶性产物。