Synthesis and characterization of TPGS-gemcitabine prodrug micelles for pancreatic cancer therapy

The therapeutic potential of a nucleoside analog, gemcitabine, is severely compromised due to its rapid clearance from systemic circulation by enzymatic degradation into an inactive metabolite. In the present investigation, micelles based on polymer-drug conjugate were developed for gemcitabine and investigated for their potential to improve cancer chemotherapy. The tocopherol poly(ethylene glycol) succinate 1000 (TPGS)-gemcitabine prodrug was synthesized via an amide linkage and characterised by analytical methods, including FT-IR, 1 H NMR, and MALDI-TOF. The micellar formulation of TPGS-gemcitabine prodrug was developed by a self-assembly technique and evaluated for various physicochemical parameters including particle size, polydispersity, morphology, critical micelle concentration and release profile. It was observed that gemcitabine present in TPGS-gemcitabine micelles was resistant to deamination by crude cytidine deaminase. The improved cytotoxicity of the micellar formulation was observed using TPGS-gemcitabine micelles against pancreatic cancer cells. Further, it was found that, unlike native gemcitabine, nucleoside transporters were not required for TPGS-Gem micelles to demonstrate their anticancer potential. These findings revealed that TPGS-gemcitabine micelles may serve as a promising platform for gemcitabine in order to improve its anticancer efficacy. Evaluation of a novel polymer-drug conjugate formulation in pancreatic cancer.