Film Dressings Based on Hydrogels: Simultaneous and Sustained-Release of Bioactive Compounds with Wound Healing Properties.

Fabian Ávila-Salas,Wendy Donoso,Gustavo Cabrera-Barjas,Gustavo Carreño,Soledad Pinochet,Adolfo Marican,Sekar Vijayakumar,Bernardo Venegas,Oscar Valdés,Esteban F Durán-Lara

doi:10.3390/pharmaceutics11090447

Fabian Ávila-Salas, Wendy Donoso + Show 8 more

Open Access

https://doi.org/10.3390/pharmaceutics11090447

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Abstract

This research proposes the rational modeling, synthesis and evaluation of film dressing hydrogels based on polyvinyl alcohol crosslinked with 20 different kinds of dicarboxylic acids. These formulations would allow the sustained release of simultaneous bioactive compounds including allantoin, resveratrol, dexpanthenol and caffeic acid as a multi-target therapy in wound healing. Interaction energy calculations and molecular dynamics simulation studies allowed evaluating the intermolecular affinity of the above bioactive compounds by hydrogels crosslinked with the different dicarboxylic acids. According to the computational results, the hydrogels crosslinked with succinic, aspartic, maleic and malic acids were selected as the best candidates to be synthesized and evaluated experimentally. These four crosslinked hydrogels were prepared and characterized by FTIR, mechanical properties, SEM and equilibrium swelling ratio. The sustained release of the bioactive compounds from the film dressing was investigated in vitro and in vivo. The in vitro results indicate a good release profile for all four analyzed bioactive compounds. More importantly, in vivo experiments suggest that prepared formulations could considerably accelerate the healing rate of artificial wounds in rats. The histological studies show that these formulations help to successfully reconstruct and thicken epidermis during 14 days of wound healing. Moreover, the four film dressings developed and exhibited excellent biocompatibility. In conclusion, the novel film dressings based on hydrogels rationally designed with combinatorial and sustained release therapy could have significant promise as dressing materials for skin wound healing.

Highlights

The primary function of the skin is to serve as a protective barrier against external hazards
20 nanopores of the polyvinyl alcohol (PVA) hydrogels crosslinked with different dicarboxylic acids were designed (Table S1)
After 5 h, the PSAH, PMALEH, PMALIH and PAAH reached about 300, 400, 500 and 600% or swelling index, respectively, at pH 7.4. This may be due to the crosslinker agent polarity, which can be explained by the available hydrophilic groups in their structure that form hydrogen bonds with water molecules

Summary

Introduction

The primary function of the skin is to serve as a protective barrier against external hazards. The loss of integrity of large portions of the skin as a result of injury or disease may lead to a major disability or even death [1,2]. Wound healing is a fundamental physiological process that restores skin integrity, aiming to repair the damaged tissues [3]. The sequence of events of wound healing has been extensively studied for several decades [4]. The mechanism of wound healing is very complex, involving several physiological events such as coagulation, inflammation, cell proliferation, matrix repair, epithelization and remodeling of the scar tissue [5]. Interruption or deregulation of one or more phases of the wound healing process leads to non-healing (chronic) wounds [6]

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