Neutron-capture therapy of murine ascites tumor with gadolinium-containing microcapsules

Summary Gadolinium-containing microcapsules were evaluated as an agent for gadolinium neutron-capture therapy. Mice were inoculated intraperitoneally with 10⁷ Ehrlich ascites tumor cells and gadolinium microcapsules and exposed to thermal neutrons for 12 min (approximately 1.86×10¹² neutrons cm^–2). Significantly more mice given gadolinium microcapsules than those given placebo microcapsules or control survived for 60 days and considerably longer (P<0.0001), indicating that gadolinium neutron-capture reactions effectively suppressed the growth of ascites tumor cells in mice. The results suggest that these microcapsules are an effective gadolinium carrier for neutron-capture therapy.Abbreviation MG meglumine gadopentetate     

Polyacrylate resin microcapsules for taste masking of antibiotics

Abstract

Various microencapsulated dosage forms were prepared to limit the release of an antibiotic in solution for up to 3 days and in the oral cavity following per oral administration. An experimental antibiotic, clarithromycin (TE-031), was used in these studies. The drug was first encapsulated in gelatin followed in some cases by crosslinking with glutaraldehyde. The gelatin microcapsules were then coated with acrylic resins (Eudragit®), whose solubility properties vary according to pH. A non-solvent coacervation technique was used to apply the Eudragit resins. It was found that crosslinking the gelatin retarded release of TE-031 somewhat relative to that from uncrosslinked gelatin microcapsules in a 72 h release experiment conducted at room temperature. Coating the gelatin microcapsules with Eudragit resins L100, S100, or E100 slowed the release of TE-031 further still; less TE-031 was released over 72 h from the Eudragit-coated formulations prepared with crosslinked gelatin compared with formulations prepared with uncrosslinked gelatin. The Eudragit ElOO-coated crosslinked gelatin microcapsule formulation was most effective in preventing release of the TE-031 under simulated conditions of storage in an aqueous solution.     

克拉霉素微囊的制备及其质量评价

目的:制备克拉霉素微囊并对其质量进行评价。方法:以乙基纤维素为囊材,采用乳化-溶剂挥发法制备克拉霉素微囊,并对微囊粒径、包封率和载药量、体外释药性进行考察。结果:所制微囊粒径分布均匀,粒径33.0～38.0μm,包封率在87%以上,载药量大于45%,6h时累积释药量达75%。结论:该制剂制备方法简便易行,质量评价合格。     

Release kinetic studies of aspirin microcapsules from ethyl cellulose, cellulose acetate phthalate and their mixtures by emulsion solvent evaporation method

The present study was oriented towards microencapsulation of aspirin and the study of its release kinetics. The desired encapsulation was achieved by emulsion solvent evaporation method using ethyl cellulose (EC), cellulose acetate phthalate (CAP) and their mixture (1:1) of polymeric constituents. Characterization of the formulations was performed by size, shape, drug loading efficiency and in-vitro drug release analysis. The in-vitro release profiles from different polymeric microcapsules were applied on different kinetic models. The prepared microcapsules were found free flowing and almost spherical in shape with particle sizes ranging from 300–700μm, having a loading efficiency of 75–85%. The best fit model with the highest correlation coefficient was observed in Higuchi model, indicating diffusion controlled principle. The n value obtained from Korsemeyer-Peppas model varied between 0.5–0.7, confirming that the mechanism of drug release was diffusion controlled. Comparative studies revealed that the release of aspirin from EC microcapsules was slower as compared to that of CAP and their binary mixture.     

Viral Microencapsulation Delays Protection after Intramuscular Inoculation of Mice with Rotavirus

Intramuscular (i.m.) immunization of mice with microencapsulated infectious rotavirus delayed protection against rotavirus challenge. Whereas unencapsulated rotavirus induced protection 6 but not 16 weeks after i.m. immunization, microencapsulated rotavirus induced protection 16 but not 6 weeks after i.m. immunization. Protection 16 weeks after immunization was associated with increased production of virus-specific immunoglobulin G (IgG) by small intestinal lamina propria (LP) lymphocytes. These findings demonstrate that i.m. immunization with microencapulated rotavirus can delay the onset of protection against challenge and the development of intestinal humoral immune responses. Simultaneous i.m. immunization with both unencapsulated and microencapsulated virus may induce prolonged protection from an intestinal pathogen, thus obviating the need for booster doses. Possible mechanisms of delayed protection induced by i.m. immunization with microencapsulated immunogens are discussed.     

APA微囊对免疫细胞和细胞因子隔离效应的研究

目的 测定海藻酸钠－多聚赖氨酸－海藻酸钠（ＡＰＡ）微囊对免疫细胞和细胞因子的隔离效应。方法 将ＮＫ细胞和ＩＬ－２、ＴＮＦ－α的活性测定方法用于微囊免疫隔离效果的评价。结果 ＮＫ细胞对微囊化Ｋ５６２靶细胞的细胞毒实验表明,微囊可有效地保护囊同细胞不受ＮＫ细胞的杀伤作用;ＩＬ－２（１５．４ｋＤ）和ＴＮＦ－α（５１ＫＤ）可通过微囊膜进入囊内,并分别支持囊内ＩＬ－２依赖细胞的生存以及对微囊内的Ｌ９２９靶细     

地塞米鬆緩釋顆粒在糖尿病性白内障手術中的應用

目的 研究Tenon’s囊下植入地塞米松缓释颗粒控制糖尿病性白内障术后前房炎症反应的有效性和安全性。方法双眼糖尿病性白内障患者37例(74眼),一眼仅于白内障术毕Tenon’s囊下植入地塞米松缓释颗粒,术后不再使用激素性眼液,作为实验组;另一眼不植入地塞米松缓释颗粒,术后常规滴典必舒眼液,作为对照组。分别观察术后1、3、7、15天的前房炎症反应、睫状充血、眼压、角膜上皮、伤口愈合状况及血糖水平等指标。结果 术后1、15天时,两组的前房炎症反应无显著性差异;术后3、7天,实验组较对照组前房炎症反应轻(P<0.05);术后1、3、7、15天,两组睫状充血评分无显著差异;两组术后各天眼压无显著性差异;地塞米松缓释颗粒对血糖、角膜上皮及伤口愈合状况无明显影响。结论 对合并糖尿病的白内障患者,术毕Tenon’s囊下植入地塞米松缓释颗粒是一种安全有效的控制术后前房炎症反应的方式。     

不同来源成体干细胞及不同细胞系的微囊化包裹

目的研究不同来源的间充质干细胞以及不同的细胞系在微囊内的存活情况,为促进骨再生微囊化基因给药平台的建立提供实验基础。方法从大鼠骨髓、脂肪和滑膜中分离培养间充质干细胞（BMSCs、ADSCs和SMSCs）,并培养C3H10T1／2、C2C12和NIH／3T3等细胞系．利用高压静电法制作包裹以上细胞的海藻酸-聚赖氨酸-海藻酸（APA）微囊．然后用EB／Calcein-AM染色方法测定细胞在微囊内1周及4周的存活情况。结果不同来源的间充质干细胞（BMSCs、ADSCs和SMSCs）以及C3H10T1／2、C2C12和NIH／3T3等细胞系在APA微囊内1周及4周的存活率均较高。结论不同来源的间充质干细胞（BMSCs、ADSCs和SMSCs）以及C3H10T1／2、C2C12和NIH／3T3等细胞系可在APA微囊内长期存活．     

壳聚糖相对分子质量对微囊及包裹肝细胞活性的影响

目的 观察壳聚糖相对分子质量对微囊机械强度和通透性及包裹肝细胞活性的影响.方法 通过微囊搅拌实验比较中、低分子量壳聚糖形成的微囊的机械强度,比较2种微囊对异硫氰酸荧光素标记的牛血清白蛋白(FITC-BSA)通透性,及细胞染色实验判断2种微囊包裹小鼠原代肝细胞活性的区别.结果 微囊搅拌100 min后中分子量壳聚糖微囊破损率100%,低分子量壳聚糖微囊破损率5%,两种微囊机械强度差异有统计学意义(P＜0.05),微囊溶液中加入HTC-BSA15 min后,低分子量壳聚糖微囊内荧光强度为4 AU,中分子量壳聚糖微囊内荧光强度为1.5 AU,两种微囊对FITC-BSA的通透性差异有统计学意义(P＜0.05),低分子量壳聚糖形成的微囊包裹肝细胞培养1周后细胞染色实验显示微囊中活肝细胞数为100%,中分子量壳聚糖形成的微囊包裹的活肝细胞数约为40%,两者差异有统计学意义(P＜0.05).结论 低分子量壳聚糖相对于中分子量壳聚糖更适合于作微囊的材料.

Abstract：

Objective To study the influence of molecular weight of chitosan on microcapsules and hepatocytes in microcapsules. Methods The mechanical strength, permeability to fluoresceine isothiocyanate-bovine serum albumin (FITC-BSA) and activity of hepatocytes in microcapsules were compared between two kinds of microcapsules made by low and middle molecular weight chitosan. Results After 100 min of stirring microcapsules, all middle molecular weight chitosan microcapsules were damaged, 5% low molecular weight chitosan microcapsules were damaged. There was significant difference in breakage rate of the mechanical strength between two microcapsules (P ＜ 0. 05). Fifteen min after addition of FITCBSA into microcapsule solution, fluorescence intensity in the low molecular weight chitosan microcapsules was 4 AU, and that in middle molecular weight of chitosan microcapsules was 1. 5 AU, suggesting there was significant difference in permeability to FITC-BSA between two kinds of microcapsules (P ＜ 0. 05).One week after culture of microencapsulated hepatocytes, staining test showed that 100% of liver cells in low molecular weight chitosan microcapsules were alive, while the number was about 40% in middle molecular weight chitosan microcapsules (P ＜ 0. 05). Conclusion Low molecular weight chitosan is more suitable as materials of microcapsules than molecular weight chitosan.     

Thermal treatment of galactose-branched polyelectrolyte microcapsules to improve drug delivery with reserved targetability

A novel multilayered drug delivery system by LbL assembly of galactosylated polyelectrolyte, which is possible to have the potential in hepatic targeting by the presence of galactose residues at the microcapsule's surface, is designed. Thermal treatment was performed on the capsules and a dramatic thermal shrinkage up to 60% decrease of capsule diameter above 50 °C was observed. This thermal behavior was then used to manipulate drug loading capacity and release rate. Heating after drug loading could seal the capsule shell, enhancing the loading capacity and reducing the release rate significantly. Excellent affinity between galactose-binding lectin and heated galactose-containing microcapsules were observed, indicating a stable targeting potential even after high temperature elevating up to 90 °C.