Temperature sensitive sol-gel transition behavior of aqueous solution of biodegradable 4arm star-shaped PLGA-PEG block copolymer

Abstract

Aqueous solution of PEO-PPO-PEO triblock copolymer has been studied as a drug delivery system since it shows temperature sensitive sol-gel transition. However, the disadvantages of this block copolymer system are the non-degradability and toxicity, which are important factors in drug delivery. In this study, biodegradable 4arm star-shaped poly((DL-lactide-co-glycolid e)-b-ethylene glycol) (4arm PLGA-PEG) copolymers were prepared with varying the molecular weight and the relative hydrophobicity of PLGA block. 4arm PLGA-PEG were synthesized by the coupling reaction of two reactive precursors, a hydroxy terminated 4arm PLGA with α-monocarboxy-ω-monome thoxy poly(ethylene glycol) (CMPEG). The resulting star-block copolymers were characterized by $^1H $ and $^13C$ nuclear magnetic resonance, gel permeation chromatography, differential scanning calorimeter and thermogravity analyzer. In high concentration solution, star-block copolymer showed temperature sensitive sol-gel transition behavior, which was confirmed by the tube tilting method. With increasing the molecular weight and the relative hydrophobicity of PLGA block, the sol-gel transition curve shifted to the left. Micellization behavior of star-block copolymer in dilute solution was investigated by UV/Visible spectrometer and dynamic light scattering. Critical micellization temperature was determined by the dye solubilization method. The effective diameter of micelle was determined by DLS. The effective diameter was highly affected by temperature. With increasing temperature, the effective diameter increased dramatically. The distribution result obtained from DLS measurement confirmed that the micelle size discretely increased due to the packing like a multi-layered lipid.