d-Gluconic acid–based methotrexate prodrug–loaded mixed micelles composed of MDR reversing copolymer: in vitro and in vivo results

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Abstract

The main aim of the present research was to synthesize carbohydrate (d-gluconic acid, DGA) prodrug of methotrexate (MTX) to improve the aqueous solubility and to develop mixed micelles (MMs) composed of d-α-tocopheryl poly (ethylene glycol) 1000 succinate (TPGS) as an MDR reversing copolymer and poloxamer 407 (P-407) to deliver the MTX prodrug to tumor tissue via enhanced permeability and retention (EPR) mechanism. MTX-DGA conjugate (MDGAC) was synthesized using Steglich esterification reaction. The MDGAC-loaded TPGS and P-407 MMs (MDGAC-TP MMs) were prepared by solvent evaporation technique. MDGAC-TP MMs showed low critical micelle concentration, high drug loading, sustained release profile, lower hemolytic behavior, higher in vitro cytotoxicity against the human carcinoma cell lines KB and MDR KBv, and significantly reduced in vivo toxicity. Therefore, the developed MDGAC-TP MMs could be a promising and effective approach for the development and treatment of MDR tumors. [Figure not available: see fulltext.].

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Kumbhar, P. S., Birange, S., Atavale, M., Disouza, J. I., & Manjappa, A. S. (2018). d-Gluconic acid–based methotrexate prodrug–loaded mixed micelles composed of MDR reversing copolymer: in vitro and in vivo results. Colloid and Polymer Science, 296(12), 1971–1981. https://doi.org/10.1007/s00396-018-4416-6

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