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

Fabián Avila-Salas,Jorge Villaseñor,Ricardo Castro,Esteban Durán-Lara,Adolfo Marican,Sergio Wehinger,Leonardo Santos,Yeray Rodriguez Nuñez

doi:10.3390/polym10070806

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 γ-cyclodextrin molecules (γ-CDPVAHMA) as systems for the controlled and sustained release of nifedipine (NFD). Through computational studies, the structural blocks (PVA chain + dicarboxylic acid + γ-CD) of 20 different hydrogels were evaluated to test their interaction energies (ΔE) with NFD. According to the ΔE obtained, the hydrogel cross-linked with maleic acid was selected. To characterize the intermolecular interactions between NFD and γ-CDPVAHMA, molecular dynamics simulation studies were carried out. Experimentally, three hydrogel formulations with different proportions of γ-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 γ-CDs linked to the hydrogels were able to form 1:1 inclusion complexes with NFD molecules. Finally, γ-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.

Highlights

Nifedipine (NFD) is calcium channel blocker of the dihydropyridine type (see its chemicalNifedipine (NFD) is calcium channel blocker of the dihydropyridine type that is principally utilized for the treatment of hypertension, angina characteristics in Table 1) that is principally utilized for the treatment of hypertension, angina pectoris pectoris and in peripheral circulatory disorders such as Raynaud’s syndrome [1]
NFD molecules undergoes a protonation of its dihydropyridine ring nitrogen at acid pH, both structures were considered for ∆E calculations
The swelling degree is a key factor in the loading and subsequent drug release the hydrogel platform

Summary

Introduction

Nifedipine (NFD) is calcium channel blocker of the dihydropyridine type (see its chemical characteristics in Table 1) that is principally utilized for the treatment of hypertension, angina characteristics in Table 1) that is principally utilized for the treatment of hypertension, angina pectoris pectoris and in peripheral circulatory disorders such as Raynaud’s syndrome [1]. Short-acting calcium antagonists are involved in the increase in sympathetic nerve calcium antagonists are involved in the increase in sympathetic nerve activation and reflex activation and reflex tachycardia. This increase may be one of the coronary risk factors in hypertensive tachycardia. This increase may be one of the coronary risk factors in hypertensive patients patients (independent of pressure) [3]

Methods

Results

Conclusion