莲子心微囊的安全性及实验性抗心律失常作用

目的初步确定莲子心微囊的安全性,研究莲子心微囊对抗心律失常的药理作用。方法本文分别采用了小鼠急性毒性实验,氯仿诱导小鼠心律失常实验模型,以及氯化钡诱导大鼠心律失常实验模型。结果小鼠最大耐受量为16.0g/kg体重;氯仿诱导小鼠心律失常实验中,微囊给药组可明显降低室颤阳性率(与空白组比较,P<0.05),氯化钡诱导大鼠心律失常实验中,微囊给药组具有明显的缩短心律失常时间和延长限定时间内心律恢复正常的持续时间的作用(与空白组比较,P<0.05),对心律恢复正常的出现时间也有提前的作用(与空白组比较,P>0.05)。结论莲子心微囊是一安全的制剂,而且初步证明其对实验性心律失常具有对抗作用。     

Inhibition of the pituitary-gonadal axis by a single intramuscular administration of D-Trp-6-LH-RH (decapeptyl) in a sustained-release formulation in patients with prostatic carcinoma

For the past 6 years we used daily injection of luteinizing hormone-releasing hormone (LH-RH) agonists to treat patients with advanced prostate carcinoma. In this study we determined the hormonal response of the pituitary-testicular axis over a 2-month period and evaluated the safety and tolerance of the single intramuscular administration of sustained-release formulations of D-Trp-6-LH-RH microcapsules designed to release 50, 100, or 200 micrograms/day for over 1 month. Serum levels of LH, testosterone, and D-Trp-6-LH-RH were measured by RIA for up to 60 days in 10 patients with advanced prostatic carcinoma who had not received any previous drug therapy. After the administration of the microcapsules there was a biphasic increase in D-Trp-6-LH-RH serum levels. The maximal peak was obtained between 1 and 3 hr, and a second peak occurred between weeks 4 and 6. LH levels increased initially, with a maximal peak at 60 min, and elevated serum LH values persisted for more than 24 hr. LH levels began to fall on the second day, reaching subnormal values after 1 week. Serum testosterone rose during the first week and fell subsequently to less than 100 ng/dl. A rebound in LH and testosterone was seen about the 50th day after the microcapsule administration. Following the first week of therapy, we observed in all patients a significant decrease in bone pain, improvement in urinary flow obstruction, and a reversal of the signs of prostatism. No side effects were observed, and acceptance of the microcapsules was very good. Our results show that a single dose of D-Trp-6-LH-RH microcapsules suppresses of the pituitary-testicular axis for at least 50 days. D-Trp-6-LH-RH microcapsules facilitate the treatment and should lead to an improvement in the therapeutic response.     

A Novel Method for Determination of Sterility of Microcapsules and Measurement of Viability of Encapsulated Organisms

A method of determining the viability of microencapsulated microorganisms (Bacillus Calmette Guerin) is reported. This method was also used to measure the effectiveness of aseptic production of mi-crocapsules in maintaining the interior of the microcapsules free from contamination by microorganisms. This method is advantageous over conventional plating methodology, as plating can only determine external contamination of microcapsules and similar devices. It involves the detection of ¹⁴CO₂, which is generated by the metabolism of ¹⁴C-labeled fatty acid in the growth medium by encapsulated microorganisms. The method depends on the semiper-meable nature of the microcapsule walls, which allows passage of ¹⁴C-palmitic acid and ¹⁴CO₂. BCG organisms encapsulated within an alginate-polylysine-alginate microcapsule (5–15 µm) (1) were shown to be viable, and no contaminating organism(s) was present. Methods suitable for the aseptic production and freeze drying of alginate–polylysine–alginate BCG microcapsules, which retain the viability of the organisms, are reported.     

In Situ Coacervated Microcapsules with Filled Polyelectrolytes and Charge‐Controlled Permeation for Dye Molecules

Microcapsules with charge‐controlled permeation for electrolytes were fabricated by an in situ coacervation method in the presence of polyelectrolyte during core removal. A layer of PAH was adsorbed onto PSS‐doped CaCO₃ microparticles, followed by crosslinking of the PAH layer with GA and core removal in a solution of EDTA with or without PAH. In the presence of PAH, microcapsules with a larger size, weight and PSS content than with PAH were obtained. Microcapsules produces without PAH showed a unique feature of charge‐controlled permeation for electrolytes: negatively charged probes were completely rejected, but positively charged ones were attracted.

     

地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。     

Improved survival of anchorage-dependent cells in core-shell hydrogel microcapsules via co-encapsulation with cell-friendly microspheres

In this study, we investigated the effect of intracapsular environment on the survival of anchorage-dependent cells (ADCs) encapsulated in alginate microcapsules with three different core structures, i.e. liquid, semi-liquid and microsphere-encapsulating semi-liquid core, using NIH 3T3 fibroblasts as an ADC model. For the latter, we fabricated poly (?-caprolactone) microspheres and co-encapsulated them with the cells, to establish cell-substrate interactions in the capsule. The fibroblast cells co-encapsulated with the microspheres exhibited higher survival and growth than those without. This study provides a “proof of concept” for employing microspheres as a cell-friendly surface to establish intracapsular cell-substrate interactions thus prolonging the survival of encapsulated therapeutic ADCs.     

芦丁微囊的制备及其质量评价

目的:研究芦丁微囊的制备工艺,并对其进行质量评价。方法:以明胶为囊材,采用单凝聚法制备芦丁微囊,通过正交设计优化其制备工艺,并对包封率、载药量、微囊的粒径分布、体外释放进行研究。结果:用本方法制备芦丁微囊的最佳工艺是明胶质量浓度为3%,囊心囊材比为1︰2,成囊温度为60℃,搅拌速度为400 r·min-1。此工艺所制得芦丁微囊的平均包封率为75.24%,有76.40%的微囊粒径分布在20～35μm,平均载药量为32.04%,体外释放在0.5 h达到30.48%,12 h累积释放达到90%以上。结论:以最佳工艺条件制备的含药微囊,重复性好,工艺稳定,同时体外释放试验表明,该微囊具有较好的缓释作用。     

Multilayered membrane-controlled microcapsules for controlled delivery of isoniazid

BACKGROUND AND THE PURPOSE OF THE STUDY: Layer-by-layer (LbL) deposition of polyelectrolytes (PEs) has received a great attention in the area of drug delivery due to its simplicity and versatility. This research was aimed to develop multilayered microcapsules through LbL deposition of chitosan (CHI) and sodium alginate (NaALG) and utilize them as vehicle for controlled delivery of isoniazid (INH). METHODS: CaCO(3) particles, prepared by colloidal crystallization of CaCl(2) and Na(2)CO(3) solutions, were used as micro-templates for LbL deposition of CHI and NaALG. Subsequent to the deposition, templates were decomposed to obtain hollow microcapsules. Prepared microcapsules were subjected to physicochemical evaluations, drug release and stability studies. RESULTS AND MAJOR CONCLUSION: Though CaCO(3) particles possessed a rough and irregular surface, prepared hollow microcapsules were spherical in shape, having smooth surface and regular thickness. Following deposition of each layer, alternating values of zeta potential were observed, indicating the formation of multilayered films. Microcapsules with 5 bilayers, i.e. (CHI/NaALG)(5) provided 39% entrapment efficiency and exhibited a controlled release behavior, lasting up to 24 hrs. An improvement in drug release rate and stability profile of the formulation was observed by increasing the number of deposition steps and performing the crosslinking of polyelectrolytes. This study showed that the prepared formulation could promisingly be utilized as controlled delivery vehicle for INH.     

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。