Paclitaxel (PTX), a taxane plant product, is one of the most effective broad-spectrum anti-cancer agents and approved for the treatment of a variety of cancers including ovarian, breast, lung, head and neck as well as Kaposi's sarcoma. Poor aqueous solubility and serious side effects associated with commercial preparation of PTX (Taxol®) triggered the development of alternative PTX formulations. Over past three decades, plethora of research work has been published towards the development of cremophor free and efficient formulations. Various nanocarrier systems including nanoparticles, liposomes, micelles, bioconjugates and dendrimers have been employed in order to improve PTX solubility and eliminate undesired side effects. These nanocarriers offer the advantage of high degree of encapsulation and cellular uptake, escape from elimination by P-glycoprotein (P-gp) mediated efflux, and can be explored for targeted drug delivery. The potential of these nanocarriers is reflected by the fact that various nanocarriers of PTX are in different stages of clinical trials and a few have already been commercialized including Abraxane®, Lipusu and Genexol PM®. This review focuses on the various challenges associated with PTX formulation development, limitations of existing formulations and novel approaches for the development of alternative formulations for PTX and also highlights the development of novel formulations in clinical settings.
The concomitant use of anticancer P-gp substrate and P-gp inhibitor is an effective and safe way to enhance the bioavailability of anticancer drugs. The poor bioavailability and toxicity of anticancer drugs limit their therapeutic efficacy. These characteristics can be improved by using various nanocarriers which exhibited a high potential to bypass this efflux protein. The best combination of P-gp inhibitor and substrate anticancer drug in a single nanocarrier formulation is a future challenge and is still probably some years away from the marketplace.
The therapeutic potential of a nucleoside analog, gemcitabine, is severely compromised due to its rapid clearance from systemic circulation by enzymatic degradation into 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 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 self-assembly technique and evaluated for various physicochemical parameters including particle size, polydispersity, morphology, critical micelle concentration and release profile. It was shown observed that gemcitabine present in TPGS-Gemcitabine micelles were resistant to deamination from crude cytidine deaminase. The improved cytotoxicity of the micellar formulation was observed by TPGS-Gemcitabine micelles against pancreatic cancer cells. Further, it was investigated that unlike native gemcitabine, the nucleoside transporters were not required for TPGS-Gem micelles to demonstrate its anticancer potential. These finding revealed that TPGS-Gemcitabine micelles may serve as a promising platform for gemcitabine in order to improve its anticancer efficacy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.