Design, synthesis, structural characterization and cell cytotoxicity of a new derivative poly(maleic anhydride-co-vinyl acetate)/miltefosine polymer/drug conjugate

In recent years, polymeric systems are selected as biomaterials because of their desired biocompatible properties and easy design/preparation of a number of different structures with lower toxicity and good solubility. Nontoxic polymeric drug carrier, maleic anhydride-co-vinyl acetate copolymer (MAVA), was prepared via free-radical chain polymerization at 80±0.1 ºC. MEK (methyl ethyl ketone) and BPO (benzoyl peroxide) were used as the organic medium and radical initiator, respectively. Copolymer was conjugated with a broad-spectrum antimicrobial agent, miltefosine (MF, an oral drug in the treatment of leishmaniosis), Impavido® and Miltex®, 1:1 molar ratio of copolymer:drug for 48 h at 60 °C in aqueous medium in presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC). Fourier transform infrared (FTIR) and nuclear magnetic resonance (1H- and 31P-NMR) were used to characterize the structure of the copolymer and MAVA/MF conjugate. Molecular weights were measured via size-exclusion chromatography (SEC). Results, obtained from the spectroscopic and SEC analysis, verified that conjugation was successfully carried out with good water-solubility. WST-1 cytotoxicity tests, 24 h by quantitative analysis, were carried out for copolymer, miltefosine, and MAVA/MF. The cytotoxicity values, by comparing with control group, were found statistically significantly different (P<0.05). MAVA/MF copolymer/drug couple was successfully designed with lower cytotoxicity than the free drug (MF).