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 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.

Sustained Release of Linezolid from Prepared Hydrogels with Polyvinyl Alcohol and Aliphatic Dicarboxylic Acids of Variable Chain Lengths

“…The release patterns of each formulation depend on the structure of the crosslinker agent, the intermolecular interactions between the linezolid drug and hydrogel network [ 12 ], and mostly on the swelling degree. Therefore, in light of the obtained outcomes, it could be deduced that the release rate of PAAH-Li was slower because the expansion of the compact network was minimal, as revealed by the water uptake process (% ESR).…”

“…Hydrogels can be of natural and/or synthetic origin [ 11 ]. Polyvinyl alcohol (PVA) hydrogels have been deeply explored due to their excellent biocompatibility properties and have been FDA (Food and Drug Administration) approved [ 12 ]. Hydrogels have received growing attention as drug delivery systems over the last decade due to their exclusive properties, such as high biocompatibility, tunable release rate, and versatility to be loaded with different molecules [ 13 , 14 ].…”

Preparation of Hydrogel/Silver Nanohybrids Mediated by Tunable-Size Silver Nanoparticles for Potential Antibacterial Applications

“…The ionic networks contain acidic pendant groups provided by the crosslinker (MAL), which have two types of pKa (pHa1 = 1.93 and pKa2 = 6.59) [26]. As has been demonstrated in previous articles, this characteristic at a certain pH provides higher ionization degree in the matrix, causing an increase of electrostatic repulsion between chains from the networks [27]. Therefore, the electrostatic repulsion generated a higher uptake of solvent into the matrix increasing the size of the hydrogel [28].…”

“…Moreover, the thermal stability was measured, where it is possible to divide the thermogram in four regions. The first region occurred between 40 and 180 °C, mainly owing to the loss of moisture and physically weak and chemically strongly bound water [27]. This is possible due to the free PVA concentration; the mass loss of three formulations was very similar (90.3%, 87.8%, and 88.4%).…”

A Liposomal Formulation for Improving Solubility and Oral Bioavailability of Nifedipine

“…However, it is a challenge to remove residual organic solvent. Therefore, novel formulations were also developed to improve therapeutic effects of nifedipine, including microparticles [9], inclusion complexes [10], freeze-dried lipid nanoparticles [7], and gelatin microcapsules [11,12].…”