Abstract
Carbamoylethyl pullulan-grafted palmitic acid (CP-g-PA), a novel self-assembled polymer was synthesized and examined for its efficacy in delivering the raloxifene (RA) to mammary carcinoma. The synthesized CP-g-PA was confirmed by evaluating through various spectral and morphological attributes. Further, the central composite design-response surface methodology with two factors at three levels was utilized to obtain the optimized and stable polymeric micelles. The optimized formulation was subjected to in vitro and in vivo evaluation. RA loaded polymeric micelles (RA-PMs) were spherical in shape with particle size less than 100 nm and high entrapment efficiency (77.02%). The developed formulation exhibited pH-dependent release profile of RA when loaded in polymeric micelles and provides substantial compatibility to erythrocytes. In vivo pharmacokinetic study demonstrates that RA-PMs offers higher mean residence time and volume of distribution as compared to pure RA. Besides, the biodistribution study manifested enhanced drug concentration in tumor and decreased concentration in other tissue as compared to pure drug. The treatment with RA-PMs also increases the median survival time, tumor inhibition rate and % increase in life span of the tumor bearing rats. Overall, the results pointed towards the overwhelming response of RA when loaded into micelles made from CP-g-PA.
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