八聚精氨酸修饰的聚乳酸-乙醇酸共聚物纳米颗粒经鼻内和静脉给药可促进洛哌丁胺向中枢神经系统的递送。
Intranasal and intravenous administration of octa-arginine modified poly(lactic-co-glycolic acid) nanoparticles facilitates central nervous system delivery of loperamide.
作者信息
O'Donnell Aisling, Moollan Azeema, Baneham Samantha, Ozgul Melike, Pabari Ritesh M, Cox Dermot, Kirby Brian P, Ramtoola Zebunnissa
机构信息
School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
出版信息
J Pharm Pharmacol. 2015 Apr;67(4):525-36. doi: 10.1111/jphp.12347. Epub 2014 Dec 17.
OBJECTIVES
The potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface modified with octa-arginine (R8) for central nervous system (CNS) delivery was investigated.
METHODS
PLGA NPs containing coumarin-6 or loperamide were surface modified using R8 and characterised for size, zeta potential, drug loading and release. We examined the cellular uptake of NPs in Madin-Darby Canine Kidney (MDCK) cells and CNS delivery of loperamide in a mouse model following intranasal (i.n.) and intravenous (i.v.) administration.
KEY FINDINGS
NPs were 300-350 nm in diameter and of negative zeta potential which neutralised on R8 conjugation. Cellular uptake of R8-PLGA NPs was rapid compared with PLGA NPs and correlated with a high antinociceptive effect in mice by both the i.n. and i.v. routes. Little antinociceptive effect for PLGA NPs was observed reflecting their slow uptake in the in-vitro cell model.
CONCLUSION
This study demonstrates the potential of R8-PLGA NPs as carriers of therapeutic agents to the CNS.
目的
研究用八聚精氨酸（R8）表面修饰的聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒（NPs）用于中枢神经系统（CNS）给药的潜力。
方法
用R8对含有香豆素-6或洛哌丁胺的PLGA NPs进行表面修饰，并对其尺寸、zeta电位、载药量和释放情况进行表征。我们检测了NPs在犬肾上皮细胞（MDCK）中的细胞摄取情况，以及在小鼠模型中经鼻内（i.n.）和静脉内（i.v.）给药后洛哌丁胺的CNS递送情况。
主要发现
NPs直径为300 - 350nm，zeta电位为负，在与R8偶联后被中和。与PLGA NPs相比，R8-PLGA NPs的细胞摄取迅速，并且通过i.n.和i.v.途径在小鼠中均表现出高抗伤害感受作用。观察到PLGA NPs的抗伤害感受作用很小，这反映了它们在体外细胞模型中的摄取缓慢。
结论
本研究证明了R8-PLGA NPs作为治疗药物向CNS递送载体的潜力。
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