Pandey Rajesh, Khuller G K
Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh-160 012, India.
J Antimicrob Chemother. 2004 Apr;53(4):635-40. doi: 10.1093/jac/dkh139. Epub 2004 Mar 3.
This study was designed to develop alginate-chitosan microspheres as drug carriers to reduce dose/dosing frequency in the management of tuberculosis (TB), which otherwise demands prolonged chemotherapy.
Alginate-chitosan microspheres encapsulating three frontline anti-tuberculous drugs (ATDs), rifampicin, isoniazid and pyrazinamide, were formulated. A therapeutic dose and a half-therapeutic dose of the microsphere-encapsulated ATDs were orally administered to guinea pigs for pharmacokinetic/chemotherapeutic evaluations, respectively.
The drug encapsulation efficiency ranged from 65% to 85% with a loading of 220-280 mg of drug per gram microspheres. Administration of a single oral dose of the microspheres to guinea pigs resulted in sustained drug levels in the plasma for 7 days and in the organs for 9 days. The half-life and mean residence time of the drugs were increased 13- to 15-fold by microsphere encapsulation, along with an enhanced relative/absolute bioavailability. The sustained release and increase in bioavailability were also observed with a sub-therapeutic dose of the microspheres. In Mycobacterium tuberculosis H37Rv-infected guinea pigs, administration of a therapeutic dose of microspheres spaced 10 days apart produced a clearance of bacilli equivalent to conventional treatment for 6 weeks. The most important observation, however, was the documentation of therapeutic benefit with a half-therapeutic dose of the microspheres administered weekly.
Alginate-chitosan microspheres hold promise as a potential natural polymer-based oral ATD carrier for better management of TB.
本研究旨在开发藻酸盐-壳聚糖微球作为药物载体，以减少结核病（TB）治疗中的剂量/给药频率，否则需要进行长时间化疗。
制备了包裹三种一线抗结核药物（ATD）利福平、异烟肼和吡嗪酰胺的藻酸盐-壳聚糖微球。分别给豚鼠口服治疗剂量和半治疗剂量的微球包裹的ATD，进行药代动力学/化疗评估。
药物包封效率在65%至85%之间，每克微球的载药量为220 - 280毫克。给豚鼠单次口服微球后，血浆中药物水平持续7天，器官中持续9天。微球包裹使药物的半衰期和平均驻留时间增加了13至15倍，同时相对/绝对生物利用度提高。给予亚治疗剂量的微球也观察到了持续释放和生物利用度增加的情况。在感染结核分枝杆菌H37Rv的豚鼠中，每隔10天给予治疗剂量的微球，产生的杆菌清除率相当于传统治疗6周的效果。然而，最重要的观察结果是记录了每周给予半治疗剂量的微球具有治疗益处。
藻酸盐-壳聚糖微球有望成为一种潜在的基于天然聚合物的口服ATD载体，用于更好地管理结核病。
