Breast cancer is a malignant tumor that grows in cells of the breast and spread (metastasize) into contiguous tissues of the body. Etiological analysis discloses that a Th1 immune response promotes secretion of acute inflammatory reactions during the initial stages of the cancer whereas Th2 response encourages tumor growth along with deactivation of cytotoxic T lymphocytes. Vitamin E has been recognized to raise Th1 type immune response, simultaneously obturating the Th2 cytokine secretion in different disease states. Paclitaxel (PTX) is utilized as first line treatment for metastatic breast cancer; however the drug is known to elicit severe adverse effects. The therapeutic benefits of PTX are further hampered by the intrinsically low aqueous solubility. In order to circumvent such pernicious trends; PTX was encapsulated in a vitamin E nanoemulsion employing high pressure homogenization to develop an immunotherapeutic nanomedicine. Developed nanoemulsion exhibited excellent encapsulation efficiency of PTX and furnished sustained drug release. Cytotoxicity study in MCF-7 cells revealed higher efficacy of PTX loaded nanoemulsion compared to marketed formulation (Taxol). PTX loaded nanoemulsion demonstrated an enhanced cell cycle arrest (G2-M phase), apoptosis and mitochondrial potential disruption in MCF-7 cells. Western blot analysis evidenced that bax, bcl-2 and caspase-3 were creditworthy for apoptotic activity of developed nanoemulsion. An enhanced secretion of IL-12 and downregulated secretion of IL-4 and IL-10 was noticed when nanoemulsion was incubated with macrophages. <i>In-vivo</i> anticancer activity demonstrated significantly enhanced efficacy of PTX loaded nanoemlsion compared to Taxol. Results of acute toxicity further substantiated the list of plausible advantages of PTX loaded nanoemulsion. Vitamin E unleashed myriad of complementary molecular effects which not only amplified anticancer activity of PTX but also showed potential of reestablishing altered natural immune response. In conclusion, developed nanomedicine would serve as viable alternative to current PTX options.

Modulation of immune response along with bax and bcl-2 mediated enhanced apoptosis in breast cancer cells via paclitaxel loaded vitamin E nanoemulsion

249th National Meeting (2015)

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