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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).
Figures and Tables
Fig. 1
In situ gel formation of the PEG/PLA multiblock copolymers aqueous solution (20 wt %). Methylene blue was added to see the gel clearly.
Fig. 2
(A) Effect of total molecular weight of PEG/PLLA multiblock copolymers (Molecular weight:Mn_ 4500 vs Mn_ 6700)) on the sol-gel transition multiblock copolymer aqueous solutions. (B) The storage modulus (G㐫) is shown as a function of temperature for the polymer aqueous solutions (25 wt %).
Fig. 3
Effect of PEG/PLLA mutiblock copolymer containing Paclitaxel on mice with HeLa tumors. (A) and (B) was the mouse from intraperitoneal injection of 1mM Paclitaxel. (C) and (D) was mouse treated with PEG/PLLA mutiblock copolymer-Paclitaxel (1 mM). Hematoxylin/Eosin-stained longitudinal sections of dorsal skin. Magnifications: ×100.
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