Production of 5–15 µm Diameter Alginate-Polylysine Microcapsules by an Air-Atomization Technique

A novel method of preparing small-sized microcapsules using a Turbotak air-atomizer is reported. Alginate-polylysine microcapsules containing Bacillus Calmette Guérin vaccine have been prepared by an adaptation of the method of Lim (1) which allows the manufacture of small-sized microcapsules. A Turbotak is used to spray sodium alginate solution into calcium chloride solution to form temporary calcium alginate microgel capsules. These temporary microgel droplets are subsequently cross-linked with polylysine to form permanent membranes. Microcapules in the size range of 5–15 µm have been produced which can be compared to an average diameter of 300 µm obtained by the method reported by Lim. The microcapsule size is dependent on the conditions of operation of the Turbotak and the concentration of the sodium alginate solution. Particles within the size range 5–15 µm can be reproducibly manufactured using the conditions of operation reported here. Other size ranges below the minimum of 300 µm reported by Lim are also feasible using this technique.     

雌二醇聚乳酸类微囊的制备与体外评价

目的　以聚乳酸或乳酸 乙醇酸共聚物为载体材料制备雌二醇缓释微囊。方法　实验中采用乳化 溶剂萃取法制备微囊 ,考察了影响微囊特性以及体外释药的各种因素 ,采用单因素试验方差分析进行因素影响的显著性检验 ,并在此基础上采用T方法进行两两间多重比较 ,进一步考察因素各水平间差异的显著性。结果　结果表明 ,粒径和加水萃取速度对雌二醇微囊的包封率有显著性影响 (P <0 0 1) ;随油相载体的浓度以及加水萃取速度对微囊的粒径影响显著 (P <0 0 1)。体外释药研究表明 ,加水萃取速度和载体的型号和分子量对微囊释药影响显著 (P <0 0 1)。但这些影响因素的各水平之间的差异性并不都具有显著性。结论　通过改变处方以及制备工艺可以得到具有不同性质的雌二醇聚乳酸类缓释微囊     

应用体内外相关性模型研究红霉素缓释微囊的体内外相关性

 目的 对红霉素缓释微囊的体内外相关性进行了研究,并对模型在预测体内数据方面的性能进行了考察。方法 应用美国缓、控释制剂专业委员会推荐的水平A、水平B两种体内外相关的模型。收集红霉素缓释微囊12 h的体外溶出数据。同时以家兔为实验动物,灌服微囊后收集血药浓度。应用水平A相关性模型,采用反卷积方法获得体内吸收百分数,并与体外溶出百分数进行比较。同时进一步运用基本的和扩展的卷积-反卷积方法对微囊的体内外相关性进行研究。对水平B相关性模型在药物相关性研究上的应用也进行了考察。结果 水平A模型和水平B模型都得到比较好的结果。结论 两种模型都能刻画体内外的相关性,水平A相关性模型可以得到较水平B相关性模型更多的关于药物体内外相关性的信息。     

天然多糖材料微囊肾动脉栓塞对肾功能和形态的影响

目的: 研究海藻酸钠-壳聚糖微囊肾动脉栓塞对肾功能和形态的影响.方法: 以天然多糖材料海藻酸钠与壳聚糖制备的海藻酸钠-壳聚糖微囊(ACM)为栓塞剂,采用经导管介入治疗技术进行兔肾动脉栓塞,于术前及术后1,2,4及8周检测血常规、肾功能及肾脏病理变化.结果: 手术前后,动物的血常规各项指标均在正常范围内波动;术后初期肾功能有所下降,1周后基本恢复正常.从血管造影与病理组织学检查结果看,健侧肾未发生任何变化,栓侧肾随栓塞时间延长出现大片弥漫性凝固性坏死,体积与重量不断减小,未出现血管再通且无侧支循环形成.结论: ACM具有良好的血管栓塞作用,使用方便,是一种较理想的血管栓塞剂.     

APA微囊包裹的牙髓干细胞成牙本质作用的研究

目的:观察海藻酸钠-多聚赖氨酸-海藻酸钠(APA)微囊包裹的牙髓干细胞移植在Scid小鼠腹腔内后成牙本质的作用,探讨APA作为牙齿组织工程支架材料的可行性。方法:用APA微囊包裹第二代人牙髓干细胞,植入Scid鼠腹腔内,植入6周后取材,通过检测被APA微囊包裹的牙髓干细胞是否表达牙本质基质特异性蛋白,观察牙本质形成情况。结果:APA微囊包裹的牙髓干细胞在植入6周后可以检测到特异性牙本质基质蛋白-牙本质涎磷蛋白的形成。结论:用APA作为支架材料,采用组织工程方法包裹的牙髓干细胞可以形成牙本质基质,牙髓干细胞和APA用于组织工程牙本质的构建具有广阔前景。     

单、复凝聚法制备酮康唑微囊的性状和包封率比较

目的:比较单、复凝聚法制备微囊的外观性状和包封率,为进一步研究微囊的制备工艺打下基础。方法:以酮康唑作为囊芯物,用明胶和阿拉伯胶作囊材,采用常规的单、复凝聚法分别制备酮康唑微囊,并在光学显微镜下比较其外观性状;采用单波长紫外分光光度法建立微囊中酮康唑含量测定方法,在此基础上计算其药物包封率。结果:2种方法所得的微囊均为白色粉末,采用单凝聚法得到的微囊平均粒径为32.20μm, 相对包封率为56.11%;复凝聚法制备的微囊则分别为7.99μm和83.42%。结论:采用相分离-凝聚法制备微囊时,复凝聚法所得结果较好。     

低分子肝素-壳聚糖-羧甲纤维素钠微囊的制备及释药性能

采用乳化分散交联法,制备了低分子肝素-壳聚糖-羧甲纤维素钠微囊,考察了不同处方工艺对微囊释药性能的影响.按最佳工艺制得的微囊形态圆整,粒径2～7μm,包封率和载药量分别为92.3%和6.47%,微囊释药具pH依赖性.兔体内释药实验的结果表明,低分子肝素微囊较注射液缓释效果明显.     

聚酰胺微胶囊对小鼠细胞的遗传毒理学研究

目的:为确保聚酰胺微胶囊的生物安全性,对其进行了急性毒性和遗传毒性试验。方法:根据《食品安全性毒性评价程序》进行小鼠经口急性毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验。结果:小鼠经口LD_(50)>50g·kg~(-1)体重,属无毒剂级,小鼠微核试验、Ames试验及小鼠精子畸形试验3项结果均为阴性。结论:受试物未见遗传毒性。     

Nano-engineered microcapsules boost the treatment of persistent pain

Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments.     

Sustained release of propranolol hydrochloride based on ion-exchange resin entrapped within polystyrene microcapsules

Propranolol-HCl, a water soluble drug, was bound to Indion 254®, a cation exchange resin, and the resulting resinate was microencapsulated with polystyrene using an oil-in-water emulsion-solvent evaporation method with a view to achieve prolonged drug release in simulated gastric and intestinal fluid. The effect of various formulation parameters on the characteristics of the microcapsules was studied. The diameter of the resinate-loaded polystyrene microcapsules increased with increase in the concentration of emulsion stabilizer and coat/core ratio and decreased with increase in the volume of organic disperse phase. The variation in the size of the microcapsules appeared to be related with the inter-facial viscosity which was influenced by the viscosity of both the aqueous dispersion medium and the organic disperse phase. The resinate encapsulation efficiency and hence the drug entrapment efficiency of the microcapsules increased with increase in the concentration of emulsion stabilizer and coat/core ratio and decreased with increase in the volume of organic disperse phase. These characteristics were found to depend on the extent of formation of fractured microcapsules and subsequent partitioning of the resinate into the aqueous dispersion medium. The degree of fracture on the microcapsules depended on the viscosity of the aqueous dispersion medium and the organic disperse phase. The uncoated resinate discharged the drug quite rapidly following the typical particle diffusion process. Although the desorption of the drug from the resinate was independent of pH of the dissolution media, increase in ionic strength increased the drug desorption. On the other hand, release of drug from the coated resinate was considerably prolonged and followed a diffusion controlled model. The prolongation of drug release was dependent on the uniformity of coating which was influenced by the formulation parameters. The drug release from the microcapsules was also found to be independent of pH of the dissolution media and increased with increase in ionic strength. The pH-independent release of the drug from both the uncoated and microencapsulated resinate was due to pH-independent solubility of the drug and high equilibrium concentration of the resinate in both the dissolution media. Polystyrene appeared to be a suitable polymer to provide prolonged release of propranolol independent of pH of the dissolution media.