期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 140, 期 -, 页码 342-352出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2015.12.044
关键词
Nanocapsule; Clozapine; Encapsulation; Macrophage; Schizophrenia
资金
- Ministry of Science [N N401 009640, JUVENTUSIP2011031571]
- European Union [POMOST/2011-4/5]
- Ministry of Science and Higher Education
- [POIG 01.02.00-069/09]
Clozapine is an effective atypical antipsychotic drug that unfortunately exhibits poor oral bioavailability. Moreover, the clinical use of the compound is limited because of its numerous unfavorable and unsafe side effects. Therefore, the aim of the present study was the development of a new nanocarrier for a more effective clozapine delivery. Here, clozapine was encapsulated into polymeric nanocapsules (NCs). Polyelectrolyte multilayer shells were constructed by the technique of sequential adsorption of poly electrolytes (LbL) using biocompatible polyanion PGA (Poly-L-glutamic acid, sodium salt) and polycation PLL (poly-L-lysine) on clozapine-loaded nanoemulsion cores. Pegylated external layers were prepared using PGA-g-PEG (PGA grafted by PEG (polyethylene glycol)). Clozapine was successfully loaded into the PLL-PGA nanocarriers (CLO-NCs) with an average size of 100 nm. In vitro analysis of the interactions of the CLO-NCs with the cells of the mononuclear phagocytic system (MPS) was conducted. Cell biocompatibility, phagocytosis potential, and cellular uptake were studied. Additionally, the biodistribution and behavioral effects of the encapsulated clozapine were also studied. The results indicate that surface modified (by PEG grafting) polymeric PLL-PGA CLO-NCs are very promising nanovehicles for improving clozapine delivery. (C) 2016 Elsevier B.V. All rights reserved.
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