Effect of topical Paclitaxel using PEG/PLGA polymer on the animal model of cervical cancer

Abstract

Objective：Paclitaxel is one of the most effective antineoplastic drugs. HPV-related cervical lesions have only managed with invasive procedure. Topical drug administration with temperature sensitive copolymer gels are useful approaches to clinical situation. In this study, we evaluated the activity of multiblock copolymers of PEG/PLA (poly(L-lactic acid)/polyethylene glycol) gels with paclitaxel (PTX) formulation administered by topical treatment to mice bearing human cervical cancer cell lines (HeLa). Methods：We have synthesized gels of PEG/PLLA (poly(L-lactic acid)/polyethylene glycol) multiblock copolymers containing Paclitaxel which have temperature-sensitivecharacteristics. This Paclitaxel-containg copolymers has the sol-gel-sol transition temperature at body temperature. The efficacy of PTX in PEG/PLA mutiblock copolymer micelle were conducted in HeLa-tumor bearing Balb/c Nu/Nu athymic mice at an equivalent paclitaxel dose of 10 mg/kg with 48 hr interval. The inhibition of tumor growth was evaluated after 8 days of treatment. Tumors were harvested at day 10 and stained with hematoxylin and eosine to measure tumor. Results：PTX-containing PEG/PLA mutiblock copolymer significantly decreased tumor growth at day 8, as measured by tumor size; ie, PEG/PLA mutiblock copolymer only goup ; 1.43±0.26 m versus intraperitoneal treatment of Paclitaxel : 0.75±0.07 mm and topical treatment of PTX-containing PEG/PLA copolymer containing Paclitaxel : 0.28 mm (Min; 0.1 mm-Max：0.8 mm). Conclusion：This demonstration that PTX-containing PEG/PLA mutiblock copolymer have a useful topical drug deliversy system carrying temperature sensitive characetersitics in HPV-related cervical lesions.