Implications of nanoscale based drug delivery systems in delivery and targeting tubulin binding agent, noscapine in cancer cells

Abstract

Noscapine, a tubulin binding anticancer agent undergoing Phase I/II clinical trials, inhibits tumor growth in nude mice bearing human xenografts of breast, lung, ovarian, brain, and prostrate origin. The analogues of noscapine like 9-bromonoscapine (EM011) are 5 to 10-fold more active than parent compound, noscapine. Noscapinoids inhibit the proliferation of cancer cells that are resistant to paclitaxel and epothilone. Noscapine also potentiated the anticancer activity of doxorubicin in a synergistic manner against triple negative breast cancer (TNBC). However, physicochemical and pharmacokinetic (ED50˜300-600 mg/kg bodyweight) limitations of noscapine present hurdle in development of commercial anticancer formulations. Therefore, objectives of the present review are to summarize the chemotherapeutic potential of noscapine and implications of nanoscale based drug delivery systems in enhancing the therapeutic efficacy of noscapine in cancer cells. We have constructed noscapine-enveloped gelatin nanoparticles, NPs and poly (ethylene glycol) grafted gelatin NPs as well as inclusion complex of noscapine in β-cyclodextrin (β-CD) and evaluated their physicochemical characteristics. The Fe3O4 NPs were also used to incorporate noscapine in its polymeric nanomatrix system where molecular weight of the polymer governed the encapsulation efficiency of drug. The enhanced noscapine delivery using μPAR-targeted optical-MR imaging trackable NPs offer a great potential for image directed targeted delivery of noscapine. Human Serum Albumin NPs (150-300 nm) as efficient noscapine drug delivery systems have also been developed for potential use in breast cancer.