Carbopol thickened nanoemulsions of chemotherapeutics to treat DMBA-induced breast cancer
Keywords:
mitoxantrone, 4-methyl umbelliferone, breast cancer, DMBA, nanoemulsion based hydrogel, hydrogelAbstract
Breast cancer is the most frequent invasive malignancy in women globally. The goal of this study was to prepare mitoxantrone and 4-methyl umbelliferone nanoemulsions followed by hydrogel preparation viz. MTO-NE-Gel and 4-MU-NE-Gel and characterized for various parameters like visual assessment, pH, rheology, ex vivo studies, and in vivo studies in 7,12-dimethylbenz(a)anthracene-induced breast cancer in swiss albino mice. The pH, viscosity, and spreadability were found to be 5.62±0.05, 13107 cP ±658, and 5.3 g.cm/s ±0.28 for 4-MU-NE-Gel and 5.75±0.03, 13025 cP ±705, and 4.06 g.cm/s ±0.45 for MTO-NE-Gel. The percent cumulative amount of drug permeated for 4-MU suspension, MTO Solution,4-MU-NE-Gel, and MTO-NE-Gel were found to be 51.26% ±5.22, 15.54% ±3.91, 89.093% ± 6.8, and 97.242%±4.51 respectively after 8 h which was significantly higher in hydrogel formulations. The outcome of pharmacodynamic studies reveals a significant reduction in tumor weight and tumor volume for MTO-NE-Gel and 4-MU-NE-Gel treated mice as compared to MTO-Gel and 4-MU-sus-Gel. Histopathological evaluation of mammary tumors indicates improvement in the tissue anatomical features and a significant decreasing trend in levels of tumor marker CA15-3 was also observed. Based on the promising results of this investigation,,,
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Abba MC, Zhong Y, Lee J, Kil H, Lu Y, Takata Y, Simper MS, Gaddis S, Shen J, Aldaz CM. DMBA induced mouse mammary tumors display high incidence of activating Pik3caH1047 and loss of function Pten mutations. Oncotarget. 2016;7(39):64289-99.
Ahmed S, Gull A, Aqil M, Ansari MD, Sultana Y. Poloxamer-407 thickened lipid colloidal system of agomelatine for brain targeting: Characterization, brain pharmacokinetic study and behavioral study on Wistar rats. Colloids Surf. B. Biointerfaces. 2019;181:426-36.
Ali HH, Hussein AA. Oral nanoemulsions of candesartan cilexetil: Formulation, characterization and in vitro drug release studies. Aaps Open. 2017;3(1):1-16.
Anzar N, Mirza MA, Anwer K, Khuroo T, Alshetaili AS, Alshahrani SM, Meena J,
Hasan N, Talegaonkar S, Panda AK. Preparation, evaluation and pharmacokinetic studies of spray dried PLGA polymeric submicron particles of simvastatin for the effective treatment of breast cancer. J. Mol. Liq. 2018;249:609-16.
Archana A, Vijayasri K, Madhurim M, Kumar C. Curcumin loaded nano cubosomal hydrogel: preparation, in vitro characterization and antibacterial activity. Chem Sci Trans. 2015;4(1):75-80.
Duffy MJ, Evoy D, McDermott EW. CA 15-3: uses and limitation as a biomarker for breast cancer. Clin. Chim. Acta. 2010;411(23-24):1869-74.
Faulds D, Balfour JA, Chrisp P, Langtry HD. Mitoxantrone. Drugs. 1991;41(3):400-49.
Faustino-Rocha A, Oliveira PA, Pinho-Oliveira J, Teixeira-Guedes C, Soares-Maia R, Da Costa RG, Colaco B, Pires MJ, Colaco J, Ferreira R. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. Lab animal. 2013;42(6):217-24.
Ghosh I, Bhattacharjee D, Das AK, Chakrabarti G, Dasgupta A, Dey SK. Diagnostic role of tumour markers CEA, CA15-3, CA19-9 and CA125 in lung cancer. Indian J. Clin. Biochem. 2013;28(1):24-29.
GLOBOCAN U. New Global Cancer Data. 2020.
Gu X, Gao Y, Wang P, Wang L, Peng H, He Y, Liu Y, Feng N. Nano-delivery systems focused on tumor microenvironment regulation and biomimetic strategies for treatment of breast cancer metastasis. Journal of Controlled Release. 2021;333:374-90.
Gull A, Ahmed S, Ahmad FJ, Nagaich U, Chandra A. Hydrogel thickened microemulsion; a local cargo for the co-delivery of cinnamaldehyde and berberine to treat acne vulgaris. J. Drug Deliv. Sci. Technol. 2020;58:101835.
Karalis TT, Heldin P, Vynios DH, Neill T, Buraschi S, Iozzo RV, Karamanos NK, Skandalis SS. Tumor-suppressive functions of 4-MU on breast cancer cells of different ER status: Regulation of hyaluronan/HAS2/CD44 and specific matrix effectors. Matrix Biol. 2019;78:118-38.
Karimi B, Ashrafi M, Shomali T, Yektaseresht A. Therapeutic effect of simvastatin on DMBA-induced breast cancer in mice. Fundam. Clin. Pharmacol. 2019;33(1):84-93.
Karimi B, Ashrafi M, Shomali T, Yektaseresht A. Therapeutic effect of simvastatin on DMBA‐induced breast cancer in mice. Fundam. Clin. Pharmacol. 2019;33(1):84-93.
Karnam KC, Ellutla M, Bodduluru LN, Kasala ER, Uppulapu SK, Kalyankumarraju M, Lahkar M. Preventive effect of berberine against DMBA-induced breast cancer in female Sprague Dawley rats. Biomed. Pharmacother. 2017;92:207-14.
Khuroo T, Verma D, Talegaonkar S, Padhi S, Panda AK, Iqbal Z. Topotecan–tamoxifen duple PLGA polymeric nanoparticles: investigation of in vitro, in vivo and cellular uptake potential. Int. J. Pharm. 2014;473(1-2):384-94.
Lazzeroni M, Serrano D, Dunn BK, Heckman-Stoddard BM, Lee O, Khan S, Decensi A. Oral low dose and topical tamoxifen for breast cancer prevention: modern approaches for an old drug. Breast Cancer Res. 2012;14(5):1-11.
Liu Y, An T, Wan D, Yu B, Fan Y, Pei X. Targets and mechanism used by cinnamaldehyde, the main active ingredient in cinnamon, in the treatment of breast cancer. Front. Pharmacol. 2020;11:1751.
Minari J. Chemopreventive effect of Annona muricata on DMBA-induced cell proliferation in the breast tissues of female albino mice. Egyptian Journal of Medical Human Genetics. 2014;15(4):327-34.
Mulia K, Ramadhan RM, Krisanti EA, editors. Formulation and characterization of nanoemulgel mangosteen extract in virgin coconut oil for topical formulation. MATEC Web of Conferences; 2018: EDP Sciences.
Multimer M. Spreadability determination by an apparatus. J Am Pharm Asso. 1956;45:212-14.
Nagy N, Kuipers HF, Frymoyer AR, Ishak HD, Bollyky JB, Wight TN, Bollyky PL. 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer. Front. Immunol. 2015;6:123.
Naz Z, Ahmad FJ. Curcumin-loaded colloidal carrier system: formulation optimization, mechanistic insight, ex vivo and in vivo evaluation. International journal of nanomedicine. 2015;10:4293.
Oktavia Indrati RM, Rohman A, Nugroho AK. Development of nanoemulsion-based hydrogel containing andrographolide: physical properties and stability evaluation. J. Pharm. Bioallied Sci. 2020;12(Suppl 2):S816.
Padhi S, Mirza MA, Verma D, Khuroo T, Panda AK, Talegaonkar S, Khar RK, Iqbal Z. Revisiting the nanoformulation design approach for effective delivery of topotecan in its stable form: An appraisal of its in vitro Behavior and tumor amelioration potential. Drug Deliv. 2016;23(8):2827-37.
Parveen S, Sahoo SK. Long circulating chitosan/PEG blended PLGA nanoparticle for tumor drug delivery. Eur. J. Pharmacol. 2011;670(2-3):372-83.
Rakha EA, Pareja FG, editors. New advances in molecular breast cancer pathology. Semin. Cancer Biol.; 2021: Elsevier.
Sabale V, Vora S. Formulation and evaluation of microemulsion-based hydrogel for topical delivery. International journal of pharmaceutical investigation. 2012;2(3):140.
Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2021). Health and treatment of diabetes mellitus. International Journal of Health Sciences, 5(1), i-v. https://doi.org/10.53730/ijhs.v5n1.2864
Tao X, Tao T, Wen Y, Yi J, He L, Huang Z, Nie Y, Yao X, Wang Y, He C. Novel delivery of mitoxantrone with hydrophobically modified pullulan nanoparticles to inhibit bladder cancer cell and the effect of nano-drug size on inhibition efficiency. Nanoscale research letters. 2018;13(1):1-12.
Tsubura A, Lai Y-C, Miki H, Sasaki T, Uehara N, Yuri T, Yoshizawa K. Animal models of N-methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials. In Vivo. 2011;25(1):11-22.
Ugwu S, Zhang A, Parmar M, Miller B, Sardone T, Peikov V, Ahmad I. Preparation, characterization, and stability of liposome-based formulations of mitoxantrone. Drug development and industrial pharmacy. 2005;31(2):223-29.
Widana, I.K., Sumetri, N.W., Sutapa, I.K., Suryasa, W. (2021). Anthropometric measures for better cardiovascular and musculoskeletal health. Computer Applications in Engineering Education, 29(3), 550–561. https://doi.org/10.1002/cae.22202
WHO. BREAST CANCER 2021 [Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer.
Available at https://www.who.int/news-room/fact-sheets/detail/breast-cancer [Accessed on 26 March 2021]
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