Łukasiewicz Sylwia, Szczepanowicz Krzysztof, Podgórna Karolina, Błasiak Ewa, Majeed Nather, Ogren Sven Ove Ögren, Nowak Witold, Warszyński Piotr, Dziedzicka-Wasylewska Marta
Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-348 Krakow, Poland.
Jerzy Haber Institute of Catalysis and Surface Chemistry PAS, 30-239 Krakow, Poland.
Colloids Surf B Biointerfaces. 2016 Apr 1;140:342-352. doi: 10.1016/j.colsurfb.2015.12.044. Epub 2016 Jan 6.
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 polyelectrolytes (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.
氯氮平是一种有效的非典型抗精神病药物，但遗憾的是其口服生物利用度较差。此外，由于该化合物存在众多不良和不安全的副作用，其临床应用受到限制。因此，本研究的目的是开发一种新型纳米载体，以更有效地递送氯氮平。在此，将氯氮平封装到聚合物纳米胶囊（NCs）中。通过使用生物相容性聚阴离子PGA（聚-L-谷氨酸钠盐）和聚阳离子PLL（聚-L-赖氨酸）在负载氯氮平的纳米乳液核上依次吸附聚电解质（层层组装，LbL）技术构建聚电解质多层壳。使用PGA-g-PEG（通过PEG（聚乙二醇）接枝的PGA）制备聚乙二醇化外层。氯氮平成功负载到平均尺寸为100 nm的PLL-PGA纳米载体（CLO-NCs）中。对CLO-NCs与单核吞噬系统（MPS）细胞的相互作用进行了体外分析。研究了细胞生物相容性、吞噬潜力和细胞摄取。此外，还研究了封装的氯氮平的生物分布和行为效应。结果表明，表面修饰（通过PEG接枝）的聚合物PLL-PGA CLO-NCs是用于改善氯氮平递送的非常有前景的纳米载体。
