Injectable controlled release depots for large molecules.
Injectable controlled release depots for large molecules.
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DOI：
10.1016/j.jconrel.2014.05.057
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发表时间：
2014-09-28
期刊：
影响因子：
--
通讯作者：
Schwendeman AS
中科院分区：
文献类型：
--
作者：
Schwendeman SP;Shah RB;Bailey BA;Schwendeman AS
用于长期控制药物释放的可生物降解的可注射贮库制剂改善了许多药物分子的治疗，并导致了十几种非常成功的药物产品。到目前为止，成功仅限于几种小分子和肽，尽管在其中一些情况下已经取得了显着的改进。例如，与溶液剂型的每日一次注射相比，亮丙瑞林的一年两次贮库型注射是可用的。注射贮库通常通过将药物封装在聚（乳酸-共-乙醇酸）（PLGA）中来制备，PLGA是一种每天在儿童中用作可吸收缝合材料的聚合物，因此具有高度生物相容性。PLGA今天仍然是美国FDA批准的肠外长效释放（LAR）产品中使用的少数“真实的世界”可生物降解的合成生物材料之一。尽管它们取得了成功，但PLGA LAR产品的更广泛使用仍然存在关键障碍，特别是用于递送更多的肽和其他大分子药物，即蛋白质。在这篇综述中，我们描述了肽和蛋白质注射PLGA控释库的发展中的关键概念，然后使用这些信息来确定阻碍PLGA库更广泛使用这类药物的关键问题。最后，我们研究了重要的方法，特别是那些在我们的研究实验室，克服这些障碍，推进商业LAR的发展。
Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.
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影响因子：
10.8
作者：
Alcock, R;Blair, JA;Quirk, AV
通讯作者：
Quirk, AV
影响因子：
10.8
作者：
Butler, SM;Tracy, MA;Tilton, RD
通讯作者：
Tilton, RD
影响因子：
16.2
作者：
Buse JB;Drucker DJ;Taylor KL;Kim T;Walsh B;Hu H;Wilhelm K;Trautmann M;Shen LZ;Porter LE;DURATION-1 Study Group
通讯作者：
DURATION-1 Study Group
影响因子：
3.8
作者：
Castellanos, IJ;Al-Azzam, W;Griebenow, K
通讯作者：
Griebenow, K
DOI：
10.1016/j.jconrel.2012.10.012
发表时间：
2013-01-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Desai KG;Schwendeman SP
通讯作者：
Schwendeman SP