O'Donnell Aisling, Moollan Azeema, Baneham Samantha, Ozgul Melike, Pabari Ritesh M, Cox Dermot, Kirby Brian P, Ramtoola Zebunnissa
School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
J Pharm Pharmacol. 2015 Apr;67(4):525-36. doi: 10.1111/jphp.12347. Epub 2014 Dec 17.
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.
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.
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.
This study demonstrates the potential of R8-PLGA NPs as carriers of therapeutic agents to the CNS.
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。
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。
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。
本研究证明了R8-PLGA NPs作为治疗药物向CNS递送载体的潜力。
