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Polyarginine nanocapsules: a new platform for intracellular drug delivery
Authors:Lozano  M V  Lollo  G  Alonso-Nocelo  M  Brea  J  Vidal  A  Torres  D  Alonso  M J
Institution:1.Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain
;2.Department of Pharmacology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain
;3.Department of Physiology, University of Santiago de Compostela, Av. Barcelona s/n, Campus Vida, Santiago de Compostela, Spain
;4.Center for Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Av. Barcelona s/n, Campus Vida, Santiago de Compostela, Spain
;5.Translational Laboratory, Medical Oncology Department, Complexo Hospitalario, Universitario de Santiago de Compostela/SERGAS, 15782, Santiago de Compostela, Spain
;
Abstract:

This report describes the development of a new nanocarrier, named as polyarginine (PArg) nanocapsules, specifically designed for overcoming cellular barriers. These nanocapsules are composed of an oily core and a PArg corona. The attachment of the PArg corona was mediated by its interaction with the oily core, which was conveniently stabilized with phosphatidylcholine. Hybrid PArg/PEG nanocapsules could also be obtained by introducing PEG-stearate in the nanocapsules formation process. The nanocapsules had an average size in the range of 120–160 nm, and a positive surface charge, which varied between +56 and +28 mV for PArg and PArg/PEG nanocapsules, respectively. They could accommodate significant amounts of lipophilic drugs, i.e., docetaxel, in their core, and also polar negatively charged molecules, i.e., plasmid DNA, on their coating. As a preliminary proof-of-principle, we explored the ability of these nanocarriers to enter cancer cells and to inhibit proliferation in the non-small cell lung cancer NCI-H460 cell line, using flow cytometry and confocal microscopy analysis. The results indicated that PArg nanocapsules are rapidly and massively accumulated into the NCI-H460 cells and that the PArg shell plays a critical role in the internalization process. Moreover, the incubation with docetaxel-loaded nanocapsules with NCI-H460 cells led to an enhanced inhibition of their proliferation, as compared to the free drug. Overall, this is the first report of the potential of PArg nanocapsules as intracellular drug delivery vehicles.

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