Zhi Kaining, Raji Babatunde, Nookala Anantha R, Khan Mohammad Moshahid, Nguyen Xuyen H, Sakshi Swarna, Pourmotabbed Tayebeh, Yallapu Murali M, Kochat Harry, Tadrous Erene, Pernell Shelby, Kumar Santosh
Plough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, 208 South Dudley Street, Memphis, TN 38163, USA.
Covance Inc., Kinsman Blvd, Madison, WI 53704, USA.
Pharmaceutics. 2021 Apr 6;13(4):500. doi: 10.3390/pharmaceutics13040500.
The blood-brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders. Poly(lactic--glycolic acid) (PLGA) is a biocompatible polymer that is used in Food and Drug Administration (FDA)-approved pharmaceutical products and medical devices. PLGA nanoparticles (NPs) have been reported to improve drug penetration across the BBB both in vitro and in vivo. Poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), and poloxamer (Pluronic) are widely used as excipients to further improve the stability and effectiveness of PLGA formulations. Peptides and other linkers can be attached on the surface of PLGA to provide targeting delivery. With the newly published guidance from the FDA and the progress of current Good Manufacturing Practice (cGMP) technologies, manufacturing PLGA NP-based drug products can be achieved with higher efficiency, larger quantity, and better quality. The translation from bench to bed is feasible with proper research, concurrent development, quality control, and regulatory assurance.
血脑屏障（BBB）是药物进入人脑的天然障碍，阻碍了对中枢神经系统（CNS）疾病的治疗，如急性缺血性中风、脑肿瘤和人类免疫缺陷病毒（HIV）-1相关神经认知障碍。聚乳酸-乙醇酸共聚物（PLGA）是一种生物相容性聚合物，用于食品药品监督管理局（FDA）批准的药品和医疗器械。据报道，PLGA纳米颗粒（NPs）在体外和体内均可提高药物透过血脑屏障的能力。聚乙二醇（PEG）、聚乙烯醇（PVA）和泊洛沙姆（普朗尼克）被广泛用作辅料，以进一步提高PLGA制剂的稳定性和有效性。肽和其他连接体可连接在PLGA表面，以实现靶向递送。随着FDA最新发布的指南以及当前良好生产规范（cGMP）技术的进步，可以更高效率、更大规模和更高质量地生产基于PLGA NPs的药品。通过适当的研究、同步开发、质量控制和监管保证，从实验室到临床的转化是可行的。
