Abstract

This work depicts the rational development (in-silico design, synthesis, characterization and in-vitro evaluation) of polyvinyl alcohol hydrogels (PVAH) cross-linked with maleic acid (MA) and linked to gamma-cyclodextrin molecules (gamma-CDPVAHMA) as systems for the controlled and sustained release of nifedipine (NFD). Through computational studies, the structural blocks (PVA chain + dicarboxylic acid + gamma-CD) of 20 different hydrogels were evaluated to test their interaction energies (Delta E) with NFD. According to the Delta E obtained, the hydrogel cross-linked with maleic acid was selected. To characterize the intermolecular interactions between NFD and gamma-CDPVAHMA, molecular dynamics simulation studies were carried out. Experimentally, three hydrogel formulations with different proportions of gamma-CD (2.43%, 3.61% and 4.76%) were synthesized and characterized. Both loading and release of NFD from the hydrogels were evaluated at acid and basic pH. The computational and experimental results show that gamma-CDs linked to the hydrogels were able to form 1:1 inclusion complexes with NFD molecules. Finally, gamma-CDPVAHMA-3 demonstrated to be the best pH-sensitive release platform for nifedipine. Its effectiveness could significantly reduce the adverse effects caused by the anticipated release of NFD in the stomach of patients.