可生物降解微球作为口服疫苗载体的研究进展

本文主要介绍可生物降解微球作为口服疫苗载体的优越性,以及微球疫苗的制备工艺、体外释放动力学、口服后的体内分布、免疫机理、口服质粒ＤＮＡ微球疫苗的研究进展。     

可生物降解微球作为口服疫苗载体的研究进展

本文主要介绍可生物降解微球作为口服疫苗载体的优越性 ,以及微球疫苗的制备工艺、体外释放动力学、口服后的体内分布、免疫机理、口服质粒 DNA微球疫苗的研究进展     

口服疫苗微球研究进展

近二十年来 ,生物技术药物 (ｂｉｏｔｅｃｈｄｒｕｇｓ)的发展突飞猛进 ,已日益受世人瞩目。其中生物技术疫苗迅速增加 ,用于癌症、艾滋病、类风湿性关节炎、镰刀形贫血、骨质疏松症、乙型肝炎及其它感染性疾病[1] 。但这类药物在口服时存在生物利用度低、物理化学稳定性差、体内半衰期短等缺点 ,致使它们常常只能采用频繁地注射给药 ,其使用与保存十分不便。口服疫苗微球则是一种有效的新制剂 ,它能满足人们对给药次数最少的需要 ,并可实现在膜表面的诱导免疫。国内对口服疫苗微球研究较少 ,本文从口服疫苗微球的特点、制备与体外释放、胃…     

PELA疫苗微球载体的正交优化工艺研究

目的：利用正交设计的数学方法进行实验设计，以牛白蛋白为包裹模型，寻求制备不同疫苗微球载体的最佳条件。方法，采用W／O／W法制备PELA微球，考察不同因素对疫苗微球平均粒径，成球率与蛋白包裹率（三指标）的影响。结果：五因素对疫苗微球成球性影响的主次顺序为PVA浓度＞搅拌速度＞PELA浓度＞油外／外水相体积比＞内水相体积；而对粒径与蛋白包裹率的顺序则为PELA浓度＞PVA浓度＞搅拌速度＞油相／外水相体积比＞内水相体积和PELA浓度＞PVA浓度＞搅拌速度＞内水相体积＞油相／外水相体积比。结论：控制工艺条件，可制备适于不同需求的疫苗微球载体。     

包裹B细胞表位的PLG微球作为口服乙型肝炎疫苗的研究

印度皮革研究所Rajkannan等将代表HBsAg B细胞表位127-145残基的多肽(BCEP)包裹人丙交醋、乙交醋共聚物( PLG)作为口服乙型肝炎疫苗进行了研究。通过W/O/W双乳剂-溶剂燕发法制备BCEP的PLG微球(BCEM),平均直径10μm,BCEP包裹效率为64%。体外释放研究结果     

壳聚糖微球的研究进展

壳聚糖是天然聚合物甲壳素脱乙酰基产物,具有独特的物理化学及生物学特征,是制备缓释、控释制剂较理想的高分子材料,已引起人们的广泛兴趣。本文综述壳聚糖微球的制备方法,影响壳聚糖微球的制备及药物释放的因素,以及壳聚糖微球的作用特点等。     

壳聚糖微球的制备及其在药物载体中的应用进展

壳聚糖因其具有独特的物理、化学及生物学特性,目前已经成为制备缓释和控释制剂的十分理想的天然高分子材料,且壳聚糖微球作为药物缓释形式也受到越来越多的关注.现综述壳聚糖徼球的缓释机制、制备方法及其在药物载体中的应用进展.     

壳聚糖微球的研究进展

壳聚糖是天然聚合物甲壳素脱乙酸基产物，具有独特的物理化学及生物学特征，是制备缓释、控释制剂较理想的高分子材料，已引起人们的广泛兴趣。本文综述壳策糖微球的制各方法，影响壳聚糖微球的制备及药物释放的因素，以及壳聚糖微球的作用特点等。     

壳聚糖微球研究进展

微球（microsphere）按制备材料分可分为淀粉微球、明胶微球、白蛋白微球、聚酯类微球、壳聚糖微球、聚乳酸微球等。壳聚糖具有多种药理活性,如抑菌、抗肿瘤、强化肝功能、降低血糖和胆固醇、抑酸、对胃肠道消化系统具有抗凝血活性、抗血栓、免疫促进作用等,这些特殊性质使壳聚糖在药物载体方面具有广阔的应用前景。     

壳聚糖微球制备方法研究

综述近年来国内外壳聚糖微球制备方法的研究进展,其中主要介绍交联法、凝聚法、乳化-溶剂蒸发法、壳聚糖溶液包衣法、壳聚糖微球乙酰化法、喷雾干燥法等。     

壳聚糖在药物缓释载体中的应用

壳聚糖是一种理化性质优良的多糖化合物。其组织相容性好,生物学活性多样,应用广泛。此文就壳聚糖在作为药物缓释载体的生物学特点,类型及研究应用方面作简要综述     

Chitosan microspheres as a potential carrier for drugs

Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, non-toxicity and mucoadhesion. It has been shown that it not only improves the dissolution of poorly soluble drugs but also exerts a significant effect on fat metabolism in the body. Gel formation can be obtained by interactions of chitosans with low molecular counterions such as polyphosphates, sulphates and crosslinking with glutaraldehyde. This gelling property of chitosan allows a wide range of applications such as coating of pharmaceuticals and food products, gel entrapment of biochemicals, plant embryo, whole cells, microorganism and algae. This review is an insight into the exploitation of the various properties of chitosan to microencapsulate drugs. Various techniques used for preparing chitosan microspheres and evaluation of these microspheres have also been reviewed. This review also includes the factors that affect the entrapment efficiency and release kinetics of drugs from chitosan microspheres.     

Development and in-vivo evaluation of insulin-loaded chitosan phthalate microspheres for oral delivery

Novel chitosan phthalate microspheres containing insulin were prepared by emulsion cross-linking technique. The feasibility of these microspheres as oral insulin delivery carriers was evaluated. The pH-responsive release behaviour of insulin from microspheres was analysed. The ability of chitosan phthalate-insulin microspheres to enhance intestinal absorption and improve the relative pharmacological availability of insulin was investigated by monitoring the plasma glucose and insulin level of streptozotocin-induced diabetic rats after oral administration of microspheres at insulin dose of 20 IU kg(-1). In simulated gastric fluid (pH 2.0), insulin release from the microspheres was very slow. However, as the pH of the medium was changed to simulated intestinal fluid (pH 7.4), a rapid release of insulin occurred. The relative pharmacological efficacy for chitosan phthalate microspheres (18.66 +/- 3.84%) was almost four-fold higher than the efficacy of the chitosan phthalate-insulin solution administration (4.08 +/- 1.52%). Chitosan phthalate microspheres sustained the plasma glucose at pre-diabetic level for at least 16 h. These findings suggest that the microsphere is a promising carrier as oral insulin delivery system.     

Optimization of chitosan succinate and chitosan phthalate microspheres for oral delivery of insulin using response surface methodology

In the present study, a Box-Behnken experimental design was employed to statistically optimize the formulation parameters of chitosan phthalate and chitosan succinate microspheres preparation. These microspheres can be useful for oral insulin delivery system. The effects of three parameters namely polymer concentration, stirring speed and cross linking agent were studied. The fitted mathematical model allowed us to plot response surfaces curves and to determine optimal preparation conditions. Results clearly indicated that the crosslinking agent was the main factor influencing the insulin loading and releasing. The in vitro results indicated that chitosan succinate microspheres need high amount of crosslinking agent to control initial burst release compared to chitosan phthalate microspheres. The reason may be attributed that chitosan succinate is more hydrophilic than chitosan phthalate. The relative pharmacological efficacy for chitosan phthalate and chitosan succinate microspheres (18.66 +/- 3.84%, 16.24 +/- 4%) was almost three-fold higher than the efficacy of the oral insulin administration (4.68 +/- 1.52%). These findings suggest that these microspheres are promising carrier for oral insulin delivery system.     

Poly(palmitoyl-l-hydroxyproline ester) microspheres as potential oral controlled drug delivery system

A new type of carrier using poly(palmitoyl-l-hydroxyproline ester) (PPH) [IUPAC name: poly((1-palmitoyl-4,2-pyrrolidinediyl)carbonyloxy)], a poly(amino acid) is described. The polymer is synthesized by conventional method and the microspheres were prepared by solvent evaporation technique for application in drug delivery system. Microspheres with different sizes were prepared by varying certain formulation and technological parameters and their distributive stabilities under physiological conditions were studied. The microspheres were characterized by DSC, optical and laser particle size analysis. A model drug, rifampicin (antituberculosis drug) was entrapped in the microspheres and the in vitro release studies were performed in pH 7.4 and pH 1.5 buffer media. The pH value seemed to have some influence on the dissolution rate of the rifampicin-containing microspheres. Dissolution experiments using rifampicin indicated the possibility of using PPH microspheres with other hydrophobic drugs.     

壳聚糖及其衍生物在胰岛素口服中的应用

壳聚糖及其衍生物可以提高胰岛素的口服生物利用度,应用广泛,发展前景广阔。本文介绍壳聚糖及其衍生物在促进胰岛素口服方面的应用进展。     

Colon-specific delivery of mesalazine chitosan microspheres

Mesalazine (5-ASA) is a cyclo-oxygenase inhibitor and anti-inflammatory drug effective in Crohn's disease and ulcerative-colitis. As 5-ASA is rapidly absorbed from the small intestine and it is necessary to develop a colon-specific delivery system for it. Coated chitosan microspheres were used for this purpose by an emulsion-solvent evaporation technique based on a multiple w/o/w emulsion. Four hundred milligrams of chitosan solution (3%) in dilute acetic acid (0.5 M) containing 12% 5-ASA was dispersed into 2 ml solution of cellulose acetate butyrate (CAB) in methylene chloride. The primary induced w/o emulsion was dispersed into a 1% PVA aqueous solution to produce a w/o/w multiple emulsion and was stirred for approximately 2.5 h. The produced microspheres were separated, washed and dried. Release of 5-ASA from microspheres was studied in different pHs 1.2, 7.4, 6.8 and 6.8 in the presence of caecal contents of rat. The average size of microspheres was 200 microm. The highest yield efficiency (80%) was seen in medium molecular weight (MW) chitosan with a 1 : 2 core/coat ratio and the greatest loading efficiency (85%) related to the microspheres of the same type of chitosan but with a 1 : 1 core/coat ratio. Decreasing the coat content and increasing chitosan Mw increased the bioadhesion significantly (p < 0.05). Microspheres of chitosan with medium Mw and 1 : 1 core/coat that showed the greatest release of drug (near 80%) in the presence of caecal secretions with a zero-order mechanism, near zero per cent in pH 1.2 after 2 h, max 20% in pH 7.4 after 3 h and near 60% in pH 6.8 after 8 h seem suitable for site-specific delivery of 5-ASA in vitro.     

Colon-specific delivery of mesalazine chitosan microspheres

Mesalazine (5-ASA) is a cyclo-oxygenase inhibitor and anti-inflammatory drug effective in Crohn's disease and ulcerative-colitis. As 5-ASA is rapidly absorbed from the small intestine and it is necessary to develop a colon-specific delivery system for it. Coated chitosan microspheres were used for this purpose by an emulsion-solvent evaporation technique based on a multiple w/o/w emulsion. Four hundred milligrams of chitosan solution (3%) in dilute acetic acid (0.5?M) containing 12% 5-ASA was dispersed into 2?ml solution of cellulose acetate butyrate (CAB) in methylene chloride. The primary induced w/o emulsion was dispersed into a 1% PVA aqueous solution to produce a w/o/w multiple emulsion and was stirred for ～2.5?h. The produced microspheres were separated, washed and dried. Release of 5-ASA from microspheres was studied in different pHs 1.2, 7.4, 6.8 and 6.8 in the presence of caecal contents of rat. The average size of microspheres was 200?µm. The highest yield efficiency (80%) was seen in medium molecular weight (MW) chitosan with a 1?:?2 core/coat ratio and the greatest loading efficiency (85%) related to the microspheres of the same type of chitosan but with a 1?:?1 core/coat ratio. Decreasing the coat content and increasing chitosan Mw increased the bioadhesion significantly (p?<?0.05). Microspheres of chitosan with medium Mw and 1?:?1 core/coat that showed the greatest release of drug (near 80%) in the presence of caecal secretions with a zero-order mechanism, near zero per cent in pH 1.2 after 2?h, max 20% in pH 7.4 after 3?h and near 60% in pH 6.8 after 8?h seem suitable for site-specific delivery of 5-ASA in vitro.     

In vitro evaluation of chondroitin sulphate-chitosan microspheres as carrier for the delivery of proteins

A novel formulation based on chondroitin sulphate/chitosan microspheres (CS/CH) has been investigated for oral delivery of macromolecules using ovalbumin as the model protein (OVA). The microspheres were prepared by a new emulsion-complex coacervation method. Physico-chemical properties of the polymers constituting microparticulate matrix were investigated by IR, DSC, TGA and X-ray diffraction analyses. In vitro tests were performed to evaluate the drug delivery system degradation and the protein release under conditions simulating the intestinal fluids. The ability of colonic enzymes to degrade the microparticulate systems was simulated employing the chondroitinase ABC enzyme. Results showed that the different CS/CH compositions influenced both microparticles stability and the protein release rate. Only the microspheres composed by 1:1 chondroitin sulphate-chitosan ratio achieved an OVA release profile suitable to a possible colon targeting. These microspheres released approximately 30% of ovalbumin encapsulated in 24 h in the different aqueous media tested, while they released 100% of protein in the presence of chondroitinase. The preliminary results demonstrated that chondroitin sulphate-chitosan microspheres can be a suitable delivery system for protein drug envisaged to oral administration.