叶酸修饰的聚乳酸及其共聚物靶向给药系统研究进展

聚乳酸及其共聚物是生物性能优良的人工聚合物,是实现药物控缓释的有效载体。近年来胶束及纳米粒形式的药物载体发展迅速。此文简要介绍了对这些纳米(亚微米)尺寸药物载体叶酸表面修饰的一般方法和取得的靶向效果。修饰后,载药粒子可以较多的选择进入叶酸受体高表达的肿瘤细胞内部,而对正常细胞影响减小,可提高药物对靶标的毒性,降低药物的副作用。另外,对几个影响药物药效的因素作了简要分析,最后结合笔者的实际工作经验,提出了尚需解决的几点问题。     

Pharmacosomes: the lipid-based new drug delivery system

Lipid-based drug delivery systems have been investigated in various studies and shown their potential in controlled and targeted drug delivery. Pharmacosomes are amphiphilic phospholipid complexes of drugs bearing active hydrogen that bind to phospholipids. Pharmacosomes impart better biopharmaceutical properties to the drug, resulting in improved bioavailability. Pharmacosomes have been prepared for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular and antineoplastic drugs. Developing the pharmacosomes of the drugs has been found to improve the absorption and minimize the gastrointestinal toxicity. This article reviews the potential of pharmacosomes as a controlled and targeted drug delivery system and highlights the methods of preparation and characterization.     

A new approach in gastroretentive drug delivery system using cholestyramine

We prepared cellulose acetate butyrate (CAB)-coated cholestyramine microcapsules as a intragastric floating drug delivery system endowed with floating ability due to the carbon dioxide generation when exposed to the gastric fluid. The microcapsules also have a mucoadhesive property. Ion-exchange resin particles can be loaded with bicarbonate followed by acetohydroxamic acid (AHA) and coated with CAB by emulsion solvent evaporation method. The drug concentration was monitored to maintain the floating property and minimum effective concentration. The effect of CAB: drug-resin ratio (2:1, 4:1, 6:1 w/w) on the particle size, floating time, and drug release was determined. Cholestyramine microcapsules were characterized for shape, surface characteristics, and size distribution; cholestyramine/acetohydroxamic acid interactions inside microcapsules were investigated by X-ray diffractometry. The buoyancy time of CAB-coated formulations was better than that of uncoated resin particles. Also, a longer floating time was observed with a higher polymer:drug resin complex ratio (6:1). With increasing coating thickness the particle size was increased but drug release rate was decreased. The drug release rate was higher in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). The in vivo mucoadhesion studies were performed with rhodamine-isothiocyanate (RITC) by fluorescent probe method. The amount of CAB-coated cholestyramine microcapsules that remained in the stomach was slightly lower than that of uncoated resin particles. Cholestyramine microcapsules were distributed throughout the stomach and exhibited prolonged gastric residence via mucoadhesion. These results suggest that CAB-coated microcapsules could be a floating as well as a mucoadhesive drug delivery system. Thus, it has promise in the treatment of Helicobacter pylori .     

A new hydrogel drug delivery system based on Hydroxyethylstarch derivatives

A new method has been developed to produce a drug delivery system (DDS) for proteins and peptides. Employing a water-in-water emulsion technique with polyethylenglycol and hydroxyethylstarch substituted by hydroxyethylmethacrylate and a subsequent photopolymerization, microspheres can be produced. This process can be carried out with proteins present in the cross-linkable phase and without the need of any organic solvents. The hydrogel microparticles are promising to fulfil the requirements for a DDS regarding biocompatibility and biodegradability.     

A new natural angelica polysaccharide based colon-specific drug delivery system

Colon-specific drug delivery systems are clinically necessary to treat colon diseases locally while minimizing systemic side effects. In this study, we extracted angelica polysaccharide from fresh roots of Angelica sinensis Diels and analyzed the monosaccharide components. With succinate as a cross-linker and angelica polysaccharide as a drug carrier, a dexamethasone–polysaccharide conjugate was synthesized. The amount of dexamethasone (Dex) loaded in the dexamethasone–polysaccharide conjugate was 14.13/100 mg. The newly synthesized dexamethasone–polysaccharide conjugate was found to greatly reduce systemic absorption of Dex and effectively deliver Dex to the large intestine. When dexamethasone–polysaccharide conjugate was used to treat TNBS-induced ulcerative colitis in rats by gavage, the ulcerative area of the colon and the colonic myeloperoxidase (MPO) activity was reduced in a dose-dependent manner. There was no effects on spleen weight, thymus weight, or peripheral blood lymphocyte count (0.25 µmol kg^?1 day^?1). These results indicate that the dexamethasone–polysaccharide conjugate has a therapeutic effect on TNBS-induced ulcerative colitis in rats, while simultaneously reducing the systemic immunosuppression caused by Dex. Thus, the angelica polysaccharide was a promising colon-specific drug carrier, and the new dexamethasone–polysaccharide conjugate may yield a potential drug for the treatment of human inflammatory bowel disease. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4756–4768, 2009     

上市新型经皮递药系统的研究进展

对近几年来上市的经皮制剂进行文献整理和归纳，通过查阅相关文献，对贴剂、软膏剂、凝胶剂、乳膏剂、泡沫剂、洗剂等经皮给药制剂的特点、上市时间、作用、不良反应等进行总结。经皮制剂是药物通过皮肤吸收的一类外用递药给药系统，可以局部给药也可以全身给药，具有安全性高、毒副作用小、使用方便的优点，是目前国内外研究的热点。     

功能化碳纳米管在药物递送系统中的应用

碳纳米管作为一种新型载体材料,具有载药量大,可以进入细胞内,实现药物的靶向运输等优点,是目前药物递送系统的研究热点之一。本文综述了碳纳米管的功能化修饰方法、载药方式、生物相容性及入胞机制方面的研究进展。     

基于碳纳米角-阿霉素的新型载药体系的制备和体外释放行为

目的制备一种以壳聚糖(CS)为修饰剂氧化单壁碳纳米角(oxSWCNHs)介导的载阿霉素(DOX)的新型药物转运系统(DOX@oxSWCNHs/CS),并考察理化性质及体外释放行为。方法制备DOX@oxSWCNHs/CS载药体系,考察体系在水、PBS、细胞培养基中的分散性,使用热重分析(TGA)、透射电镜(TEM)、紫外可见吸收光谱、荧光光谱、zeta电位对其理化性质进行考察,评价其体外释放效果。结果 DOX通过π-π堆积作用装载于oxSWCNHs上,载药量达60%;用CS修饰oxSWCNHs的疏水表面,可增加oxSWCNHs在水溶液中的分散性,特别是在盐溶液中分散性。载药体系的体外释放具有pH依赖性和缓释效果。结论 oxSWCNHs能够作为一种潜在的阿霉素载体达到药物的缓释效果。     

快速增长的释药系统品种

2005年在美国零售额前200个品牌药品中,年增长率超过100％的有11个,其中释药系统有6个;零售额前200个通用名药品中逾1亿美元,年增长率100％以上的有6个,其中释药系统有2个（见表1）。     

多重响应的介孔碳载药体系的制备与初步评价

目的 为了能更好的使药物作用于肿瘤部位,同时减少药物对其他部位的毒副作用,研究制备了近红外(near infrared,NIR)、pH 和还原多重响应型的介孔碳(mesoporous carbon nanoparticles,MCN)药物递送系统.方法 研究将聚丙烯酸(polyacrylic acid,PAA)通过二硫...     

多单元胃漂浮给药系统研究进展

胃漂浮给药系统可以增加药物在胃中的滞留时间，从而增加药物的吸收，提高药物的生物利用度。按药物剂量的分配方式，胃漂浮给药系统可分为“一单元”和“多单元”给药系统（如微丸、微球等）。“多单元”较“一单元”胃漂浮给药系统有着药物释放吸收的个体差异小、可避免药物剂量的“全或无”现象、对胃刺激性小、可以将不同释放速率的药物单元组合等优点。本文介绍了目前国内外多单元胃漂浮给药系统的类型、制备方法、释药情况及其体内漂浮性能的研究方法。     

Periodontal delivery of ipriflavone: new chitosan/PLGA film delivery system for a lipophilic drug

The aim of the present work was to design a film dosage form for sustained delivery of ipriflavone into the periodontal pocket.For this purpose, monolayer composite systems made of ipriflavone loaded poly(D,L-lactide-co-glycolide) (PLGA) micromatrices in a chitosan film form, were obtained by emulsification/casting/evaporation technique. Multilayer films, made of three layers of polymers (chitosan/PLGA/chitosan), were also prepared and compared to monolayer films for their "in vitro" characteristics. Morphology and physico-chemical properties of the different systems were evaluated. The influence of pH, ionic strength and enzymatic activity on film degradation, was also investigated. Significant differences in swelling, degradation and drug release were highlighted, depending on film structure and composition. In vitro experiments demonstrated that the composite micromatricial films represent a suitable dosage form to prolong ipriflavone release for 20 days.     

新型抗血吸虫药物QH917自微乳化释药系统的优化和评价

筛选新型抗血吸虫药物QH917自微乳化释药系统的处方。以油相的用量(%)和表面活性剂与助表面活性剂的质量比(K_m)作为自变量，自乳化时间(t)、平均粒径(PS)和多分散系数(PI)作为因变量，采用星点设计——效应面法进行处方优化，模拟体内环境，考察了离子强度、食物、pH值、转速和介质体积对优化处方释放的影响，并采用大鼠在体小肠吸收试验评价了优化处方的吸收情况。结果表明，优化处方为：油相中链甘油三酸酯(MCT)的质量分数为30%～34%，表面活性剂聚氧乙烯40氢化蓖麻油(Cremophor RH40)与助表面活性剂乙醇的质量比为4.8～5.2。优化处方的释放行为基本不受介质环境的影响。大鼠在体小肠吸收试验表明胆管结扎与未结扎对吸收率无显著影响，个体间吸收行为差异性较小。以星点设计——效应面法对自微乳化释药系统的处方进行优化，预测性良好，优化处方体外释放和大鼠小肠吸收行为均比较稳定。     

Tyrosinase inhibitor-loaded microsponge drug delivery system: new approach for hyperpigmentation disorders

Objective: The aim of the present investigation was to design and formulate appropriate form of glabridin, using microsponge drug delivery system. Method: Microsponges were prepared by emulsion solvent evaporation method and characterized by drug loading, infrared spectroscopy and scanning electron microscopy. In?vitro diffusion studies of gel formulation were performed using ethanol: phosphate buffer (1:1) mixture as receptor medium. Animal studies were carried out using brownish guinea pigs with UV-induced pigmentation model. Results: Prepared microsponges were predominantly yellowish, free-flowing and spherical in shape. The infrared spectra revealed the absence of drug polymer interaction. Scanning electron microscopy (SEM) and porosity studies confirmed spherical and porous nature. In?vitro release studies data depicted highest correlation with Higuchi treatment. Animal studies also supported the better depigmenting activity as compared to plain gel. Conclusion: Glabridin microsponge-loaded gel could be efficacious in treating various hyperpigmentation disorders.     

Nasal drug delivery: new developments and strategies

The use of the nasal route for the delivery of challenging drugs has created much interest in recent years in the pharmaceutical industry. Consequently, drug delivery companies are actively pursuing the development of novel nasal drug-delivery systems and the exploitation of these for administration of conventional generic drugs and peptides, both in-house and with partners in the pharmaceutical industry. This review sets out to discuss some new developments and strategies in nasal drug delivery. An exiting discovery that drugs can be transported directly from nose to brain via the olfactory pathway is discussed and examples of proof-of-concept in man are given.     

Application of ultrasound energy as a new drug delivery system

Ultrasound is frequently used in medicine for diagnostic purposes. Recently, there have been numerous reports on application of ultrasound energy for controlling drug release or targeting. This new concept of therapeutic ultrasound combined with drugs has induced excitement in various areas. Ultrasound energy can enhance effects of thrombolytic agents as urokinase. Ultrasound emitting catheters are currently being developed for cardiovascular diseases. Device with ultrasound transducers implanted in transdermal drug patches are also being evaluated for possible delivery of insulin through the skin. Chemical activation of drugs by ultrasound energy for treatment of cancers is another new field recently termed as "Sonodynamic Therapy". Various examples of application of ultrasound for drug delivery systems are discussed.     

A novel in situ forming drug delivery system for controlled parenteral drug delivery

The objective of this study was to investigate the in vitro drug (diltiazem hydrochloride and buserelin acetate) release from different in situ forming biodegradable drug delivery systems, namely polymer solutions (in situ implants) and in situ microparticle (ISM) systems. The drug release from ISM systems [poly(d,l-lactide) (PLA) or poly(d,l-lactide-co-glycolide) (PLGA)-solution dispersed into an external oil phase] was investigated as a function of the type of solvent and polymer, polymer concentration and internal polymer phase:external oil phase ratio and was compared to the drug release from in situ implant systems and microparticles prepared by conventional methods (solvent evaporation or film grinding). Upon contact with the release medium, the internal polymer phase of the ISM system solidified and formed microparticles. The initial drug release from ISM systems decreased with increasing polymer concentration and decreasing polymer phase:external oil phase ratio. The type of biocompatible solvent also affected the drug release. It decreased in the rank order DMSO>NMP>2-pyrrolidone. In contrast to the release of the low molecular weight diltiazem hydrochloride, the peptide release (buserelin acetate) was strongly dependent on the polymer degradation/erosion. One advantage of the ISM system when compared to in situ implant systems was the significantly reduced burst effect because of the presence of an external oil phase. ISM systems resulted in drug release profiles comparable to the drug release of microparticles prepared by the solvent evaporation method. Therefore, the ISM systems are an attractive alternative to existing complicated microencapsulation methods.