A difunctional Pluronic®127-basedin situformed injectable thermogels as prolonged and controlled curcumin depot, fabrication,in vitrocharacterization andin vivosafety evaluation

Curcumin has been reported to be used widely against many types of pathological conditions in clinics. However due to its limitations such as poor solubility, poor oral absorption and low stability has limited its applications. In current study, a series of novel chemically cross-linkable depot gel formulations were developed based on thermoresponsive micellar polymer (Pluronic®127) with polyelectrolyte hydrophilic monomer i.e. 2-acrylamido-2-methylpropane sulfonic acid by cold and insitu grafting polymerization method. The formulations were aimed to deliver curcumin at controlled rate from insitu formed depot after administration through subcutaneous route invivo. The sol-gel phase transitions of formulations were observed by rheological analysis, tube titling and optical transmittance measurements. Maximum swelling of gel formulations was observed at pH 7.4 and below CGT i.e. 25 °C. The invitro release profile exhibit maximum drug release at pH 7.4 and 25 °C owing to relaxed gel state. Invitro degradation profile of gel formulations showed controlled degradation rate. Cells growth inhibition study confirmed the biocompatibility and safe nature of bare gel formulations against L929 cell lines. Invitro cytotoxic study showed that curcumin loaded in gel formulation has controlled pharmacological activity against HeLa and MCF-7 cancer cells as compared to free drug solution. The IC50 values calculated for pure curcumin solution (30 ± 0.77 µg/ml for HeLa and 27 ± 0.39 µg/ml for MCF-7) were found higher in comparison to curcumin loaded thermogels; against HeLa (19 ± 0.28 µg/ml and 23 ± 0.81 µg/ml) and MCF-7 (22 ± 0.54 µg/ml and 21 ± 0.49 µg/ml). Histopathological and Haematological analysis showed the biocompatible nature of hydrogels. Structural confirmation was done by Fourier transformed infra-red spectroscopy (FTIR) and proton nuclear magnetic resonance spectroscopy (1HNMR). Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed the thermal stability of the gel formulation. The porous structure of gel formulations was assessed by scanning electron microscopic (SEM) analysis. Results concluded that newly developed gel formulations has thermoresponsive behavior with phase transition at body temperature and can be used as insitu controlled drug depot.