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控释淀粉-脂质植入物治疗重症疟疾。

Controlled release starch-lipid implant for the therapy of severe malaria.

机构信息

Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 3, 06120 Halle (Saale), Germany.

Roquette Freres, route haute loge, 62080 Lestrem, France.

出版信息

Int J Pharm. 2022 Jun 25;622:121879. doi: 10.1016/j.ijpharm.2022.121879. Epub 2022 May 29.

Abstract

Parenteral depot systems can provide a constant release of drugs over a few days to months. Poly-(lactic acid) (PLA) and Poly-(lactide-co-glycolide) (PLGA) are the most commonly used polymers in the production of these systems. Finding alternatives to these polymers is of great importance to avoid certain drawbacks of these polymers (e.g. microacidity) and to increase the selection possibilities. In this study, different types of starch in combination with glycerol monostearate (GMS) were developed and investigated for their physicochemical properties and release characteristics. The noninvasive method of electron paramagnetic resonance (EPR) was used to study the release kinetics and mechanisms of nitroxide model drugs. The studies demonstrated the general suitability of the system composed of high amylose starch and GMS to form a controlled release system. For further characterization of the prepared system, formulations with different proportions of starch and GMS, loaded with the antimalarial agents artesunate or artemether were prepared. The implants were characterized with X-ray powder diffraction (XRPD) and texture analysis. The in vitro release studies demonstrated the sustained release of artemether over 6 days from a starch-based implant which matches desired kinetic for the treatment of severe malaria. In summary, a starch-based implant with appropriate mechanical properties was produced that can be a potential candidate for the treatment of severe malaria.

摘要

注射储库系统可以在数天至数月内持续释放药物。聚(乳酸)(PLA)和聚(乳酸-共-乙醇酸)(PLGA)是生产这些系统中最常用的聚合物。寻找这些聚合物的替代品非常重要,以避免这些聚合物的某些缺点(例如微酸性)并增加选择可能性。在这项研究中,开发了不同类型的淀粉与甘油单硬脂酸酯(GMS)组合,并研究了它们的物理化学性质和释放特性。非侵入性的电子顺磁共振(EPR)方法用于研究氮氧自由基模型药物的释放动力学和机制。研究表明,高直链淀粉淀粉和 GMS 组成的系统通常适合形成控制释放系统。为了进一步表征制备的系统,用抗疟药青蒿琥酯或青蒿素制备了具有不同淀粉和 GMS 比例的制剂。用 X 射线粉末衍射(XRPD)和织构分析对植入物进行了表征。体外释放研究表明,基于淀粉的植入物中青蒿素持续释放 6 天,这与治疗重症疟疾的理想动力学相匹配。总之,生产出了具有适当机械性能的淀粉基植入物,它可能成为治疗重症疟疾的潜在候选药物。

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