453Hydrogels are polymer-based systems that embrace numerous biomedical and pharmaceutical applications. Much interest has been focused on polymer systems that show a phase transition in response to temperature. 1) Pluronic F127 (PF127) or Poloxamer 407 is non-ionic, polyoxyethylenepolyoxypropylene-polyoxyethylene tri-block copolymers which form micelles at low concentrations and clear, thermoreversible hydrogels at concentration above 20%.2) When injected into a body cavity, the gel preparation forms a solid artificial barrier and a sustained release depot.3) PF127 systems can prolong drug release which is one of the very few synthetic polymeric materials approved by the U.S. Food and Drug Administration for use as food additives and pharmaceutical ingredients. Potential drawbacks of PF127 hydrogels include their weak mechanical strength, rapid erosion, and the non-biodegradability. 4) To circumvent these problems, PF127 can be chemically modified by other polymers. Chemical modifications of copolymers not only improve the properties of the polymers but also impart new and more attractive properties of them.The use of natural polymers such as proteins and polysaccharides for biomedical application has attracted much investigation. Hyaluronic acid (HA) is an attractive building block for new biocompatible and biodegradable polymers with applications in drug delivery, tissue engineering, and also viscosupplementation to restore lubrication in osteoarthritic knee joints.5) It is a natural-occurring linear polysaccharide. In this study, HA grafted with PF127 was prepared as a thermosensitive material (HP) for heterogeneously-structured formulation composed of drug reservoir. There are two investigations which prepare the HP composite as the delivery vehicles of human growth hormone and ciprofloxacin.6,7) The synthetic method used was photo-polymerization or chemical reaction. Although the sol-gel temperature and drug release behaviors are examined previously, however, the physicochemical characterization of the hydrogels such as polarity, viscosity, and microstructural appearance are not fully explored. The aim of this study was to elucidate the correlation of theses physicochemical properties related to drug release. Two platinum drugs, cisplatin and carboplatin ( Fig. 1), were used as the model drugs loaded in hydrogels because of their short half-lives and toxicity in human body.
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ExperimentalMaterials Cisplatin, carboplatin, Nile red, and Pluronic F127 (PF127, polyoxyethylene-polyoxypropylene-polyoxyethylene tri-block copolymer, molecular weightϭ12.5 kDa, lot number 103K0058) were purchased from Sigma Chemical (St. Louis, MO, U.S.A.). 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC, lot number A0219466) and N-hydroxylsuccinimide (NHS, lot number A0188987001) were obtained from Acros Organics (Geel, Belgium). Hyaluronic acid (HA) was produced from Streptococcus zooepidemicus by a method described by Armstrong and Johns.9) The molecular weight of HA was 1780 kDa (polydispersityϭ1.68) determined by size excl...