Immunotherapeutic vitamin E nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response

Vivek K. Pawar, Samir B. Panchal, Yuvraj Singh, Jaya Gopal Meher, Komal Sharma, Pankaj Singh,Himangshu K. Bora, Akhilesh Singh, Dipak Datta, Manish K.Chourasia Journal of Controlled Release 196, 295–306 (2014)

Speaker: Pei-Chun Li (李姵君)                                 Time: 13:10~14:00, May 13, 2015

Commentator: Dr. Chih-Peng Chang (張志鵬老師)    Place: Room 601

Abstract:

　　Paclitaxel (PTX) is used as first line treatment for metastatic breast cancer but has a heavy cost in terms of accompanying adverse effects. Furthermore, effective delivery of PTX to cancer cell in any mode is a challenging task. Clinical success attained post-Taxol dosing is relative which depends on the extent of adverse effects, but it is a routine policy to co-administer an anti-allergen to partially diminishing the serious hypersensitivity reactions. Therefore, there is no such counter-plot to tackle the haemolytic potential of Taxol. The authors used high pressure homogenization to incorporate PTX in a vitamin E nanoemulsion. Compared to free PTX and marketed formulation (Taxol), PTX loaded nanoemulsion exhibited higher cytotoxicity in breast cancer cell line (MCF-7). The advantages of PTX nanoemulsification was further substantiated by acceptable haemolytic potential. Cell cycle arrest study with MCF-7 cells treated with PTX loaded nanoemulsionshowed high arrest in G2-Mphase. Cytokine estimation study in macrophages showed that both PTX loaded nanoemulsion and blank nanoemulsion enhanced secretion of IL-12 and downregulatedsecretion of IL-4 and IL-10. In-vivo anticancer activity showed significantly improved efficacy of PTX loaded nanoemlsion compare to Taxol and free PTX. Results suggest that inclusion of vitamin E in nanoemulsion opened multiple complementary molecular effects which not only magnified the principle antiproliferative activity of PTX but also independently showcased potential in restoring the proactive nature of the breast cancer immune response. In conclusion, developed nanoemulsion could also modulate the tumor cell immunology to retard the chronic tumor growth, and PTX loaded vitamin E nanoemulsion would improve the chemotherapy of breast cancer by improved efficacy and reduced toxicity of drug.

Reference:

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