Fabrication of self-assembled chitosan-dispersed LDL nanoparticles for drug delivery with a one-step green method

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• 作者：Jing Tian^a ; Shasha Xu^a ; Hongbing Deng^b ; ^{hbdeng@whu.edu.cn} ; Xinxing Song^c ; Xiujuan Li^c ; Jiajia Chen^b ; Feng Cao^c ; ^{wind8828@gmail.com} ; Bin Li^a ; ^{libinfood@mail.hzau.edu.cn}
• 关键词：Low-density lipoprotein ; Chitosan ; Self-assembly ; Nanocarrier
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：25-34
• 全文大小：2792 K
• 卷排序：517

文摘

Self-assembled nanoparticles (NPs) composed of chitosan (CS) and low density lipoprotein (LDL) of hen eggs were prepared by a one-step green synthesis of mixing CS solution and LDL suspension. The formulated CS-LDL NPs were then applied to encapsulate doxorubicin hydrochloride (DOX) with the encapsulation efficiency of 51.7%. The average particle size and ζ-potential of DOX-loaded CS-LDL NPs (CS-LDL-DOX NPs) were 179 nm and +48.3 mV, respectively. The encapsulated DOX showed less cytotoxicity than free DOX after 24-h incubation with gastric cancer SGC7901 cells, which may be due to extended release. Cellular uptake of CS-LDL-DOX NPs was significant higher than that of free DOX due to the endocytosis of tumor cells. Thus CS-LDL-DOX NPs showed a potential in reducing cytotoxicity of DOX by extended release behavior and preferential uptake compared to free DOX. In addition, flow cytometry and terminal-deoxynucleotidyl-transferase-mediated dUTP nick-end labeling assay demonstrated that CS-LDL-DOX NPs induced the apoptosis of cancer cells. Autophagy was involved in effects caused by CS-LDL-DOX NPs through blocking AKT/mTOR signaling, which was demonstrated by the analyses of the expression of LC3, p62, AKT, p-AKT, mTOR and p-mTOR.