Novel biomimetic nanocomposite for investigation of drug metabolism

Balogh Weiser, Diána and Poppe, László and Kenéz, Balázs and Decsi, Balázs and Koplányi, Gábor and Katona, Gábor and Gyarmati, Benjámin Sándor and Ender, Ferenc and Balogh, György Tibor (2022) Novel biomimetic nanocomposite for investigation of drug metabolism. JOURNAL OF MOLECULAR LIQUIDS, 368 (Part B). No. 120781. ISSN 0167-7322

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Abstract

In vitro mimicking of hepatic drug metabolism is a key issue in early-stage drug discovery. Synthetic metalloporphyrins show structural similarity with the heme type prosthetic group of cytochrome P450 as primary hepatic enzyme in oxidative drug biotransformation. Therefore, they can catalyze these oxidations. Concerning economical aspects and the poor stability of metalloporphyrin, their immobilization onto or into solid carriers can be promising solution. This study presents a novel immobilized metalloporphyrin nanocomposite system and its potential use as biomimetic catalysts. The developed two-step immobilization procedure consists of two main steps. First, the ionic binding of meso-tetra (parasulphonatophenyl) iron porphyrin onto functionalized magnetic nanoparticles is established, followed by embedding the nanoparticles into polylactic acid nanofibers by electrospinning technique. Due to the synergistic morphological and chemo-structural advantages of binding onto nanoparticles and embedding in polymeric matrices the biomimetic efficiency of metalloporphyrin can be remarkably enhanced, while substrate conversion value was tenfold larger than which could be achieved with classic human liver microsomal system.

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