期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 589, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2020.119776
关键词
Nasal delivery; PLGA/chitosan nanoparticles; Ropinirole; Mucoadhesion; Cytotoxicity; Ex vivo permeability
资金
- European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme
- European Regional Development Fund (ERDF), through the COMPETE 2020 Operational Programme for Competitiveness and Internationalization
- Portuguese national funds via FCT Fundacao para a Glenda e Tecnologia [PROSAFE/O 001/2016, POCI-01-0145-FE DER-030331, UIDB/04539/2020]
Nose-to-brain delivery is an attractive route for direct drug delivery to the central nervous system (CNS), avoiding hepatic first-pass metabolism and solving blood-brain barrier passage issues. Therefore, the aim of the present study was the development of PLGA and PLGA/chitosan (chit) nanoparticles (NPs) with mucoadhesive properties, able to encapsulate ropinirole hydrochloride (RH), an anti-Parkinsonian dopaminergic agonist, and suitable to promote RH delivery across the nasal mucosa. NPs produced by nanoprecipitation showed spherical shape and a mean average size of 98.8 nm and 468.0 nm (PLGA and PLGA/chit, respectively). RH loaded PLGA/chit NPs showed a complete release of the drug in simulated nasal electrolyte solution (SNES) over the period of 24 h and increased the permeation of RH through sheep nasal mucosa by 3.22-fold in comparison to PLGA NPs. None of RH loaded NPs induced hemolysis in whole blood or the production of reactive oxygen species (ROS) in Raw 264.7 cells. On their turn, PLGA/chit NPs decreased cell viability of Raw 264.7 cells and Peripheral Blood Mononuclear Cells (PBMCs) in a concentrationdependent manner. These results revealed that, particularly PLGA/chit NPs, could be a valuable carrier for the delivery of RH to the CNS, opening a new path for Parkinson's disease therapy.
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