title: Tumor-targeted paclitaxel-loaded folate conjugated poly(ethylene glycol)-poly(L-lactide) microparticles produced by supercritical fluid technology.
abstract: The new biodegradable diblock copolymers poly(ethylene glycol)-poly(L-lactide) (PEG-PLLA) were synthesized and were chemically conjugated with folate (FA) in the PEG terminal ends to form FA-PEG-PLLA. Then the hydrophobic drug paclitaxel (PTX) loaded microparticles (PTX/FA-PEG-PLLA) were produced via solution enhanced dispersion by supercritical fluids (SEDS). These microparticles exhibited sphere-like shape by scanning electron microscopy observation and showed narrow hydrodynamic size distributions by dynamic light scattering measurement. Drug loading of PTX loaded microparticles was about 7-9% and the encapsulation efficiency of PTX loaded microparticles was about 18-23%. Flow cytometry and confocal laser scanning microscope analyses revealed that fluorescein isothiocyanate labeled FA conjugated microparticles presented significantly higher cellular uptake than FA-free group due to the FA-receptor-mediated endocytosis. In vitro cytotoxicity evaluation indicated that FA-PEG-PLLA expressed negligible cytotoxicity to mouse fibroblasts L929 cells. Moreover, PTX/FA-PEG-PLLA microparticles exhibited much higher anti-cancer efficacy than PTX/PEG-PLLA microparticles against human ovarian cancer SKOV3 cells. Nude mice xenografted with SKOV3 cells were used in biodistribution studies, the results indicated that an increased amount of PTX was accumulated in the tumor tissue deal with PTX/FA-PEG-PLLA microparticles. These results collectively suggested that PTX/FA-PEG-PLLA microparticles prepared by SEDS would have potential in anti-tumor applications as a tumor-targeted drug delivery formulation.
authors: College of Materials Science and Engineering, Sichuan University, Chengdu, 610064, People's Republic of China.
authors: Xiaobei
authors: X
authors: Huang
authors: Yanzhi
authors: Y
authors: Zhang
authors: Guangfu
authors: G
authors: Yin
authors: Ximing
authors: X
authors: Pu
authors: Xiaoming
authors: X
authors: Liao
authors: Zhongbing
authors: Z
authors: Huang
authors: Xianchun
authors: X
authors: Chen
authors: Yadong
authors: Y
authors: Yao
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002460:Cell Line; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007773:Lactates / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D007773:Lactates; D011091:Polyesters; C534468:poly(lactic acid)-block-polyethylene glycol-folate; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D017239:Paclitaxel
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