Rational Development of a Novel Hydrogel as a pH-Sensitive Controlled Release System for Nifedipine

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.

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.