In vitro &in vivo targeting behaviors of biotinylated Pluronic F127/poly(lactic acid) nanoparticles through biotin–avidin interaction

• Published in: European journal of pharmaceutical sciences Vol. 46; no. 5; pp. 537 - 544
• Main Authors: Xiong, Xiang Yuan, Guo, Liang, Gong, Yan Chun, Li, Zi Ling, Li, Yu Ping, Liu, Zhi Yong, Zhou, Ming
• Format: Journal Article
• Language: English
• Published: Kindlington Elsevier B.V 15.08.2012; Elsevier
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - metabolism; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Avidin - administration & dosage; Avidin - metabolism; Biological and medical sciences; Biotin; Biotinylation; CA-125 Antigen - immunology; Cell Line, Tumor; Cell Survival - drug effects; Chemistry, Pharmaceutical; Drug Carriers; Female; General pharmacology; Humans; Injections, Intraperitoneal; Kinetics; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Fluorescence; Nanoparticle; Nanoparticles; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - immunology; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Paclitaxel - metabolism; Paclitaxel - pharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pluronics; Poloxamer - chemistry; Poly(lactic acid); Solubility; Targeted drug delivery; Technology, Pharmaceutical - methods; Tumor Burden - drug effects; Xenograft Model Antitumor Assays; Poly(lactic acid); Targeted drug delivery; Biotin; Pluronics; Nanoparticle; Targeting; Targeted therapy; Vehicle(excipient); Surfactant polymer; Drug carrier; B-Vitamins; Laxative; Lactone polymer; Avidin; Target; Targeted drug; Aliphatic polymer; Microparticle; Behavior; Amphiphilic polymer; Pharmaceutical technology; Non ionic surfactant; Interaction; In vitro; In vivo; Triblock copolymer; Lactic acid polymer; Poloxamer
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2012.04.011

Biotinylated Pluronic F127/poly(lactic acid) block copolymers (B-F127–PLA) were successfully synthesized previously by our group. In the present study, the release behaviors of paclitaxel-loaded B-F127–PLA nanoparticles and their targeting properties to human ovarian carcinoma cells were investigated. Paclitaxel (pac) loaded in B-F127–PLA nanoparticles shows an initial burst release in the first 6h and followed by a slow release. The in vitro targeting behaviors of B-F127–PLA nanoparticles against human ovarian cancer cells (OVCAR-3, SKOV-3) were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM) technique. Targeting was based on a three-step biotin–avidin targeting approach using biotinylated anti-CA125 antibody specific for the CA-125 antigen that is highly expressed on OVCAR-3 cells but not expressed on SKOV-3 cells. MTT results show that the anticancer effect of paclitaxel in B-F127–PLA nanoparticles over OVCAR-3 cells was stronger than that over SKOV-3 cells, indicating that B-F127–PLA nanoparticles were delivered more effectively to OVCAR-3 cells than to SKOV-3 cells. The targeting behaviors of B-F127–PLA nanoparticles were further confirmed by FM technique. The intracellular distribution of B-F127–PLA nanoparticles was also studied using a triple-labeling method. It was observed that B-F127–PLA nanoparticles are mainly localized within the cytoplasm of OVCAR-3 cells. The in vivo antitumor efficacy of pac-loaded B-F127–PLA nanoparticles by three-step method as measured by change in tumor volume of OVCAR-3 implanted in Balb/C nude mice was greater than that by one-step method.