Abstract
Development of efficient ocular drug delivery systems was still a challenging task. The objective of this article was to develop a thermosensitive PEG–PCL–PEG (PECE) hydrogel and investigate its potential application for ocular drug delivery of diclofenac sodium (DIC). PECE block polymers were synthesized by coupling MPEG-PCL co-polymer using IPDI reagent, and then its sol–gel transition as a function with temperature was investigated by a rheometer. The results showed that 30% (w/v) PECE aqueous solution exhibited sol–gel transition at approximately 35 °C. In vitro release profiles showed the entrapped DIC was sustained release from PECE hydrogels up to 7 days and the initial drug loading greatly effect on release behavior of DIC from PECE hydrogels. MTT assay results indicated that no matter PECE or 0.1% (w/v) DIC-loaded PECE hydrogels were nontoxic to HCEC and L929 cells after 24 h culturing. In vivo eye irritation test showed that the instillation of either 30% (w/v) PECE hydrogels or 0.1% (w/v) DIC-loaded PECE hydrogels to rabbit eye did not result in eye irritation within 72 h. In vivo results showed that the AUC0–48 h of 0.1% (w/v) DIC-loaded PECE hydrogels exhibited 1.6-fold increment as compared with that of commercial 0.1% (w/v) DIC eye drops, suggesting the better ophthalmic bioavailability could be obtained by the instillation of 0.1% (w/v) DIC-loaded PECE hydrogels.
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