Issues in long-term protein delivery using biodegradable microparticles
Issues in long-term protein delivery using biodegradable microparticles
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DOI：
10.1016/j.jconrel.2010.05.011
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发表时间：
2010-09-01
影响因子：
10.8
通讯作者：
Park, Kinam
中科院分区：
文献类型：
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作者：
Ye, Mingli;Kim, Sungwon;Park, Kinam
近年来，随着生物技术的进步，多种生物活性蛋白药物已大量上市。这种可用性促进了长期蛋白质递送系统的开发。可生物降解的微粒系统已广泛用于蛋白质药物的控制释放数天和数月。最广泛使用的生物可降解聚合物是聚(D,L-乳酸-乙醇酸) (PLGA)。含蛋白质微粒通常通过水/油/水（W/O/W）双乳化法制备，并且也使用该方法的变体，例如固体/油/水（5/O/W）和水/油/油（W/O/O）。其他制备方法包括喷雾干燥、超声雾化和电喷雾方法。开发用于蛋白质药物递送的可生物降解微粒的重要因素是蛋白质释放曲线（包括突发释放、释放持续时间和释放程度）、微粒大小、蛋白质负载、包封效率和释放蛋白质的生物活性。许多研究使用白蛋白作为模型蛋白，因此，释放蛋白的生物活性尚未得到检验。其他利用酶、胰岛素、促红细胞生成素和生长因子的研究表明，在加工和储存步骤中保持负载蛋白质药物的生物活性的正确配方非常重要。各种微粒制剂的蛋白质释放曲线可分为四个不同的类别（A、B、C 和 D 型）。这些类别基于突发释放的程度、蛋白质释放的程度以及突发释放之后的蛋白质释放动力学。各种微粒中的蛋白质负载量（即蛋白质负载总量除以微粒总重量）为6.7+/-4.6%，范围为0.5%至20.0%。开发基于可生物降解微粒的临床成功的长期蛋白质递送系统需要提高药物装载效率、初始爆发释放的控制以及控制蛋白质释放动力学的能力。 (C) 2010 Elsevier B.V. 保留所有权利。
Recently, a variety of bioactive protein drugs have been available in large quantities as a result of advances in biotechnology. Such availability has prompted development of long-term protein delivery systems. Biodegradable microparticulate systems have been used widely for controlled release of protein drugs for days and months. The most widely used biodegradable polymer has been poly(D,L-lactic-co-glycolic acid) (PLGA). Protein-containing microparticles are usually prepared by the water/oil/water (W/O/W) double emulsion method, and variations of this method, such as solid/oil/water (5/O/W) and water/oil/oil (W/O/O), have also been used. Other methods of preparation include spray drying, ultrasonic atomization, and electrospray methods.The important factors in developing biodegradable microparticles for protein drug delivery are protein release profile (including burst release, duration of release, and extent of release), microparticle size, protein loading, encapsulation efficiency, and bioactivity of the released protein. Many studies used albumin as a model protein, and thus, the bioactivity of the release protein has not been examined. Other studies which utilized enzymes, insulin, erythropoietin, and growth factors have suggested that the right formulation to preserve bioactivity of the loaded protein drug during the processing and storage steps is important. The protein release profiles from various microparticle formulations can be classified into four distinct categories (Types A, B, C, and D). The categories are based on the magnitude of burst release, the extent of protein release, and the protein release kinetics followed by the burst release. The protein loading (i.e., the total amount of protein loaded divided by the total weight of microparticles) in various microparticles is 6.7 +/- 4.6%, and it ranges from 0.5% to 20.0%. Development of clinically successful long-term protein delivery systems based on biodegradable microparticles requires improvement in the drug loading efficiency, control of the initial burst release, and the ability to control the protein release kinetics. (C) 2010 Elsevier B.V. All rights reserved.