Surface modification of PLGA nanoparticles with biotinylated chitosan for the sustained in vitro release and the enhanced cytotoxicity of epirubicin

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2016-02, Vol.138, p.1-9
• Main Authors: Chen, Hongli, Xie, Li Qin, Qin, Jingwen, Jia, Yajing, Cai, Xinhua, Nan, WenBin, Yang, Wancai, Lv, Feng, Zhang, Qi Qing
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacokinetics; Antibiotics, Antineoplastic - pharmacology; Biotin; Biotinylation; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carbocyanines - chemistry; Cell Survival - drug effects; Cellular; Chitosan; Chitosan - chemistry; Drug delivery systems; Drugs; Encapsulation; Endocytosis; Epbrubicin; Epirubicin - chemistry; Epirubicin - pharmacokinetics; Epirubicin - pharmacology; Humans; In vitro testing; Kinetics; Lactic Acid - chemistry; MCF-7 Cells; Mice, Nude; Microscopy, Confocal; Microscopy, Electron, Scanning; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Particle Size; Photoelectron Spectroscopy; PLGA nanoparticle; Polyglycolic Acid - chemistry; Surface Properties; Uptakes; Xenograft Model Antitumor Assays
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2015.11.033

[Display omitted] •We successfully prepared Bio-CS-PLGA NPs with active functional group of biotin on their surface.•Bio-CS-PLGA NPs exhibited a greater extent of cellular uptake.•Bio-CS-PLGA NPs were able to enter into cancer cells via biotin receptor endocytosis.•Bio-CS-PLGA NPs were mainly distributed in the tumor after 24h post administration. In this study, poly(d,l-lactide-co-glycolide) nanoparticles (PLGA NPs) with biotinylated chitosan (Bio-CS)-surface modification were prepared to be usded as a tumor-targeted and prolonged delivery system for anticancer drugs. Epirubicin (EPB), as a model drug, was encapsulated into Bio-CS surface modified PLGA (Bio-CS-PLGA) NPs with a drug encapsulation efficiency of 84.1 ± 3.4%. EPB-loaded Bio-CS-PLGA NPs were spherical shaped, and had a larger size and higher positive zeta potential compared to the unmodfied EPB-loaded PLGA NPs. The in vitro drug releases showed that EPB-loaded Bio-CS-PLGA NPs exhibited relatively constant drug release kinetics during the first 48 h and the drug burst release significantly decreased in comparison to the unmodified PLGA NPs. The results of MTS assays showed that Bio-CS-PLGA NPs markedly increased the cytotoxicity of EPB, compared to both the unmodified PLGA NPs and the CS-PLGA NPs. The uptakes of NPs in human breast cancer MCF-7 cells were evaluated by the flow cytometry and the confocal microscope. The results revealed that Bio-CS-PLGA NPs exhibited a greater extent of cellular uptake than the unmodified PLGA NPs and CS-PLGA NPs. Moreover, the cellular uptake of Bio-CS-PLGA NPs was evidently inhibited by the endocytic inhibitors and the receptor ligand, indicating that biotin receptor-mediated endocytosis was perhaps involved in the cell entry of Bio-CS-PLGA NPs. In MCF-7 tumor-bearing nude mice, EPB-loaded Bio-CS-PLGA NPs were efficiently accumulated in the tumors. In summary, Bio-CS-PLGA NPs displayed great potential for application as the carriers of anticancer drugs.