School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland; Department of Pharmacology, PU-RCSI School of Medicine, Perdana University, Selangor, Malaysia.
J Pharm Pharmacol. 2013 Oct;65(10):1473-81. doi: 10.1111/jphp.12125. Epub 2013 Aug 1.
In this study, we examined the relative cellular uptake of nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA) polymers with increasing degree of pegylation (PLGA-PEG) and their potential to deliver loperamide to the brain of a mouse.
NPs containing coumarin-6 or loperamide HCl were formulated using PLGA and PLGA-PEG, with PEG content of 5-15%, by the solvent evaporation method. NPs were characterised for size, surface charge, morphology, encapsulation efficiency and drug release. Cellular uptake of coumarin-6 NPs was examined in Caco-2 monolayers using confocal microscopy and central nervous system (CNS) delivery of loperamide HCl from the NPs was examined following intranasal administration in a mouse model.
No difference in NP characteristics was observed, irrespective of degree of pegylation, except for the surface charge which increased with increasing PEG content. PLGA-PEG NPs were found to have increased cellular uptake in comparison to PLGA NPs. Interestingly, this pattern was reflected in the CNS delivery of loperamide HCl in the mouse model.
The results from this study show that PLGA-PEG NPs have the potential to act as carriers for the noninvasive administration of therapeutic agents to the brain and possibly across other physiological barriers.
在这项研究中，我们研究了使用聚（乳酸-共-乙醇酸）（PLGA）聚合物与不同程度的聚乙二醇化（PLGA-PEG）制备的纳米颗粒（NPs）的相对细胞摄取及其将洛哌丁胺递送至小鼠大脑的潜力。
通过溶剂蒸发法，使用 PLGA 和 PLGA-PEG（PEG 含量为 5-15%）制备了含有香豆素-6 或盐酸洛哌丁胺的 NPs。对 NPs 的大小、表面电荷、形态、包封效率和药物释放进行了表征。通过共聚焦显微镜研究了 Caco-2 单层中香豆素-6 NPs 的细胞摄取，并在小鼠模型中通过鼻内给药研究了 NPs 中盐酸洛哌丁胺对中枢神经系统（CNS）的递送。
除了表面电荷随 PEG 含量增加而增加外，无论 PEG 化程度如何，NPs 的特性均无差异。与 PLGA NPs 相比，PLGA-PEG NPs 的细胞摄取量增加。有趣的是，这种模式反映在小鼠模型中盐酸洛哌丁胺对 CNS 的递送中。
本研究结果表明，PLGA-PEG NPs 有可能作为非侵入性给药载体，将治疗剂递送至大脑，并可能递送至其他生理屏障。
