期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 67, 期 4, 页码 525-536出版社
WILEY-BLACKWELL
DOI: 10.1111/jphp.12347
关键词
central nervous system delivery; loperamide; nanoparticles; octa-arginine; PLGA
资金
- Science Foundation Ireland (SFI)
ObjectivesThe potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface modified with octa-arginine (R8) for central nervous system (CNS) delivery was investigated. MethodsPLGA 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 findingsNPs were 300-350nm 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. ConclusionThis study demonstrates the potential of R8-PLGA NPs as carriers of therapeutic agents to the CNS.
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