title: Biotin-Conjugated Multilayer Poly [D,L-lactide-co-glycolide]-Lecithin-Polyethylene Glycol Nanoparticles for Targeted Delivery of Doxorubicin.
abstract: Multilayer nanoparticle combining the merits of liposome and polymer nanoparticle has been designed for the targeted delivery of doxorubicin (DOX) in cancer treatment. In this study, DOX-PLGA-lecithin-PEG-biotin nanoparticles (DOX-PLPB-NPs) were fabricated and functionalized with biotin for specific tumor targeting. Under the transmission electron microscopy observation, the lipid layer was found to be coated on the polymer core. The physical characteristics of PLPB-NPs were also evaluated. The confocal laser scanning microscopy confirmed the cellular uptake of nanoparticles and targeted delivery PLPB-NPs. The in vitro release experiment demonstrated a pH-depending release of DOX from drug-loaded PLPB-NPs. Cytotoxicity studies in HepG2 cells and in vivo antitumor experiment in tumor-bearing mice both proved DOX-PLPB-NPs showed the best inhibition effect of tumor proliferation. In biodistribution studies, DOX-PLPB-NPs showed a higher DOX concentration than free DOX and DOX-PLGA-lecithin-PEG nanoparticles (DOX-PLP-NPs) in tumor site, especially in 24 h, and the lowest DOX level in normal organs. The results were coincident with the strongest antitumor ability showed among in vivo antitumor experiment. Histopathology analysis demonstrated that DOX-PLPB-NPs exhibited the strongest antitumor ability and lowest cardiotoxicity. In brief, the PLPB-NPs were proved to be an efficient delivery system for tumor-targeting treatment.
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China.
authors.forename: Han
authors.initials: H
authors.lastname: Xing
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China.
authors.forename: Fuling
authors.initials: F
authors.lastname: Song
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China.
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Lu
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu Province 210009, China.
authors.forename: Shuangxia
authors.initials: S
authors.lastname: Ren
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China. Electronic address: chenxj-lab@hotmail.com.
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China. Electronic address: ningli656@cpu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001710:Biotin / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D054709:Lecithins / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D054709:Lecithins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D001710:Biotin; D004317:Doxorubicin
keywords: PLGA; distribution; liposomes; nanoparticles; pegylation; targeted drug delivery