Targeted delivery of paclitaxel using folate-decorated poly(lactide)–vitamin E TPGS nanoparticles

• Published in: Biomaterials 2008-06, Vol.29 (17), p.2663-2672
• Main Authors: Pan, Jie, Feng, Si-Shen
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - therapeutic use; Biodegradable polymers; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer nanotechnology; Cell Line, Tumor; Cell Survival - drug effects; Dentistry; Drug Delivery Systems; Female; Folic Acid - chemistry; Folic Acid - metabolism; Humans; Molecular Structure; Nanobiotechnology; Nanomedicine; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Nanotechnology - methods; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Paclitaxel - metabolism; Paclitaxel - therapeutic use; Particle Size; Polyesters - chemical synthesis; Polyesters - chemistry; Polyesters - metabolism; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polyethylene Glycols - metabolism; Spectrum Analysis - methods; Vitamin E - analogs & derivatives; Vitamin E - chemical synthesis; Vitamin E - chemistry; Vitamin E - metabolism
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2008.02.020

Abstract We synthesized nanoparticles (NPs) of the blend of two-component copolymers for targeted chemotherapy with paclitaxel used as model drug. One component is poly(lactide)– d -α-tocopheryl polyethylene glycol succinate (PLA–TPGS), which is of desired hydrophobic–lipophilic balance, and another is TPGS–COOH, which facilitates the folate conjugation for targeting. The nanoparticles of the two-copolymer blend at various component ratio were prepared by the solvent extraction/evaporation single emulsion method and then decorated by folate, which were characterized by laser light scattering (LLS) for particles' size and size distribution, zeta potential analyzer for surface charge, and X-ray photoelectron spectroscopy (XPS) for surface chemistry. The drug encapsulation efficiency (EE) and in vitro drug release were measured by high performance liquid chromatography (HPLC). The targeting effect was investigated in vitro by cancer cell uptake of coumarin-6-loaded NPs and further confirmed by cytotoxicity of cancer cells treated with the drug formulated in the NPs. We showed that the NP formulation has great advantages vs the pristine drug in achieving better therapeutic effect, which increased 8.68% for MCF-7 breast cancer cells, and that the folate-decoration can significantly promote targeted delivery of the drug into the corresponding cancer cells and thus enhance its therapeutic effect, which increased 24.4% for the NP formulation of 16.7% TPGS–COOH component and 31.1% for the NP formulation of 33.3% TPGS–COOH component after 24 h treatment at the same 25 μg/ml paclitaxel concentration. The experiments on C6 glioma cells further confirmed these advantages.