Emre ÖZGENÇ, Evren GÜNDOĞDU

Development of freeze-dry kits containing imatinib and different chelating agents: characterization, stability and cytotoxicity studies

The current study aims to develop new freeze-dry kits containing Imatinib and different chelating agents for breast cancer treatment and diagnosis as theranostics. Four formulations (Kit-1, Kit-2, Kit-3, and Kit-4) were prepared, and the characterization of formulations was assessed utilizing particle size, polydispersity index, zeta potential, fourier transform infra-red analysis, ultraviolet spectrum analysis, differential calorimetry, and thermogravimetric analysis. They were also evaluated for stability at different storage conditions and cytotoxicity effect on fibroblast NIH-3T3 cells. The particle size, polydispersity index, and zeta potential of developed formulations were found to be between 6953.6 ±131.6 and 5888.3 ± 131.6 nm, 0.481 ± 0.24 and 0.319 ± 0.18, -594.5±59.6 and -477.3 ± 25.32 mV, respectively. Fourier transform infra-red analysis, ultraviolet spectrum, differential calorimetry, and thermogravimetric analysis have proven that IMT and chelating agents formed complexes in kit formulations. Also, they exhibited stable facility and above 90% of cell viability on fibroblast NIH-3T3 cells. By the result of our study, kit formulations can be a favorable drug delivery system in the treatment and diagnosis of breast cancer with a non-toxic effect on healthy cells.

PDF

___

[1] Cohen Martin H, Williams G, Johnson JR, Duan J, Gobburu J, Rahman A, Benson K, Leighton J, Kim SK, Wood R, Rothmann M, Chen G, Khin Maung U, Staten AM, Pazdur R. Approval Summary for Imatinib Mesylate Capsules in the Treatment of Chronic Myelogenous Leukemia. Clin Cancer Res. 2002; 8(5): 935–942.
[2] Waller CF. Imatinib Mesylate. Recent Results in Cancer Res. 2018; 212: 1-27. [CrossRef]
[3] Sumer B, Gao J. Theranostic nanomedicine for cancer. Nanomedicine (Lond). 2008; 3(2): 137-140. [CrossRef]
[4] Haque MA, Vasudha BD, Surekha B, Gouthami C, Hari Priya R, Yakamma B. Development of uv-spectrophotometric method for the determination of imatinib mesylate in bulk and formulation. Int J Pharm Res Health Sci. 2016; 4(2): 1130–1135.
[5] Danaei MM, Dehghankhold SA, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, M. R. Mozafari SMR. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018; 10(2): 57. [CrossRef]
[6] Bhojya Naik H, Siddaramaiah S, Ramappa PG. Thermogravimetric analysis of Cobalt(II)-Dothiepin complexes. J Therm Anal Calorim. 1999; 55(3): 841–49. [CrossRef]
[7] Guimarães KL, Inês Ré M. Lipid nanoparticles as carriers for cosmetic ingredients: The first (SLN) and the second generation (NLC). In: Beck R, Guterres S, Pohlmann A. (Eds). Nanocosmetics and Nanomedicines New Approaches For Skin Care. Springer, Verlag Berlin Heidelberg, 2011 pp. 101–122.
[8] Imatinib, DrugBank Online. https://go.drugbank.com/drugs/DB00619 (accessed on 1 March 2021).
[9] Gundogdu E,Karasulu HY, Koksal C, Karasulu E. The novel oral imatinib microemulsions: Physical properties, cytotoxicity activities and improved Caco-2 cell permeability. J Microencapsul Micro and Nano Carriers. 2013; 30(2): 132-142.
[10] Othman MF, Elise V, Costa I, Tanapirakgul M, Cooper MS, Imberti C, Lewington VJ, Blower PJ, Terry SYA. In vitro cytotoxicity of auger electron-emitting [67Ga]Ga-Trastuzumab. Nucl Med Biol. 2020; 80(81): 57–64. [CrossRef]
[11] Mohini G, Sharma R, Amirdhanayagam J, Sarma HD, Rangarajan V, Dash A, Das T. Formulation and clinical translation of [177Lu] Lu-Trastuzumab for radioimmunotheranostics of metastatic breast cancer. RSC Med Chem. 2021;12: 263-277. [CrossRef]
[12] International Atomic Energy Agency. Development of kits for 99mTc radiopharmaceuticals for infection imaging, IAEA-TECDOC-1414, IAEA, Vienna. 2004.
[13] Smita JP, Rajendra CD, Priya PD. Development of uv-spectrophotometric method for the determination of imatinib mesylate (ITM) in Bulk and Formulation. Asian J Pharm Clin Res. 2013; 6(3): 54–57.
[14] Bożena K, Górniak A, Marciniak DM, Mucha I. Molecular mobility and stability studies of amorphous imatinib mesylate. Pharmaceutics. 2019; 11(7): 304. [CrossRef]
[15] Maude R, Wiest J, Saedtler M, Harlacher C, Gutmann M, Zottnick SH, Piechon P, Dix I, Buschbaum KM, Holzgrabe U, Meinel L, Galli B. Bioinspired co-crystals of imatinib providing enhanced kinetic solubility. Eur J Pharm Biopharm. 2018; 128: 290–299. [CrossRef]