In-vitro release study of Pt(II) and Fe(III) metallocefotaxime drug candidates in pH dependent releasing mediums mimicking human biological fluids

Cefotaxime (CFT), a third-generation broad-spectrum cephalosporin antibiotic against gram-positive and gram-negative bacterial infections, inhibits bacteria's cell wall synthesis by binding to the targets of cephalosporin. Pharmacological properties and biological activity of cephalosporins are quite higher when they are in the form of metal complexes. Inspired by the superior pharmacokinetics and biological activities of metallocefotaxime drug candidates, the present study is the first attempt to investigate the in-vitro releasing profiles of Pt-CFT and Fe-CFT drug complexes. To that aim, a crosslinked free-radical polymerized poly(acrylic acid) (PAA) based hydrogel system was prepared, then release of CFT, Pt-CFT, and Fe-CFT were examined at 37°C in pH dependent releasing mediums mimicking enzyme-free human stomach (pH 1.2), intestine (pH 7.4), and physiological body fluid (pH 7.4). Degree of swelling and release profiles of metal-CFT complexes from the PAA hydrogel was compared to CFT. In-vitro antimicrobial activity of CFT, Pt-CFT, and Fe-CFT was tested by agar disc-diffusion method. It has been observed that all hydrogel systems except for that of high weight percentages of N,N-methylenebisacrylamide:Acrylic Acid loaded with low quantity of Fe-CFT responded to all studied releasing medium. Scanning Electron Microscopy images of drug loaded hydrogels have shown that the distribution of the loading material in the hydrogel matrix is quite uniform. All the studied hydrogel systems show the highest SR% in SPF (pH 7.4) medium. As a result, PAA-based hydrogel matrixes prepared in this work have the potential to act as a suitable drug carrier for the delivery of CFT, Pt-CFT, and Fe-CFT drug candidates.