title: Immunotherapeutic vitamin E nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response.
abstract: Paclitaxel (PTX) is used as first line treatment for metastatic breast cancer but the relief comes at a heavy cost in terms of accompanying adverse effects. The pharmaceutical credentials of PTX are further dampened by the intrinsically low aqueous solubility. In order to sideline such insidious tendencies, PTX was incorporated in a vitamin E nanoemulsion using high pressure homogenization. The encapsulation efficiency of PTX in nanoemulsion was 97.81±2.7% and a sustained drug release profile was obtained. PTX loaded nanoemulsion exhibited higher cytotoxicity in breast cancer cell line (MCF-7) when compared to free PTX and marketed formulation (Taxol). Cell cycle arrest study depicted that MCF-7 cells treated with PTX loaded nanoemulsion showed high arrest in G2-M phase. Moreover blank nanoemulsion induced additional apoptosis in breast cancer cells through G1-S arrest by disrupting mitochondrial membrane potential. Cytokine estimation study in macrophages showed that both PTX loaded nanoemulsion and blank nanoemulsion enhanced secretion of IL-12 and downregulated secretion of IL-4 and IL-10. 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 slackened chronic immune response. In-vivo anticancer activity showed significantly improved efficacy of PTX loaded nanoemlsion compare to Taxol and free PTX. The list of plausible advantages of PTX nanoemulsification was further substantiated by acceptable haemolytic potential, reduced in-vivo toxicity and conveniently modified pharmacokinetic profile in which the AUC and MRT were extended considerably. Overall, there were strong evidences that developed formulation can serve as a viable alternative to currently available PTX options.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Pawar
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Samir B
authors.initials: SB
authors.lastname: Panchal
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Yuvraj
authors.initials: Y
authors.lastname: Singh
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Jaya Gopal
authors.initials: JG
authors.lastname: Meher
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Komal
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Singh
authors.affiliation: Laboratory Animals Facility, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Himangshu K
authors.initials: HK
authors.lastname: Bora
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Singh
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India.
authors.forename: Dipak
authors.initials: D
authors.lastname: Datta
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India. Electronic address: manish_chourasia@cdri.res.in.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Chourasia
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004339:Drug Compounding; D004655:Emulsions; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D014810:Vitamin E / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D004655:Emulsions; D014810:Vitamin E; D017239:Paclitaxel
keywords: Apoptosis; Cell cycle arrest; Cytokine; Cytotoxicity; Taxol