Polyvinylidene fluoride-Hyaluronic acid wound dressing comprised of ionic liquids for controlled drug delivery and dual therapeutic behavior
authors Abednejad, A; Ghaee, A; Morais, ES; Sharma, M; Neves, BM; Freire, MG; Nourmohammadi, J; Mehrizi, AA
nationality International
journal ACTA BIOMATERIALIA
author keywords Active pharmaceutical ingredients; Ionic liquids; Dual function; Drug release; Polyvinylidene fluoride; Hyaluronic acid; Bilayer wound dressing
keywords VITRO SKIN PERMEATION; SURFACE MODIFICATION; ANTIBACTERIAL ACTIVITY; POTENTIAL APPLICATION; THERMAL-STABILITY; CROSS-LINKING; PVDF MEMBRANE; HYDROGELS; SODIUM; NANOPARTICLES
abstract To improve the efficacy of transdermal drug delivery systems, the physical and chemical properties of drugs need to be optimized to better penetrate into the stratum corneum and to better diffuse into the epidermis and dermis layers. Accordingly, dual-biological function ionic liquids composed of active pharmaceutical ingredients were synthesized, comprising both analgesic and anti-inflammatory properties, by combining a cation derived from lidocaine and anions derived from hydrophobic nonsteroidal anti-inflammatory drugs. Active pharmaceutical ingredient ionic liquids (API-ILs) were characterized through nuclear magnetic resonance, cytotoxicity assay, and water solubility assay. All properties were compared with those of the original drugs. By converting the analgesic and anti-inflammatory drugs into dual-function API-ILs, their water solubility increased up to 470-fold, without affecting their cytotoxic profile. These API-ILs were incorporated into a bilayer wound dressing composed of a hydrophobic polyvinylidene fluoride (PVDF) membrane to act as a drug reservoir and a biocompatible hyaluronic acid (HA) layer. The prepared bilayer wound dressing was characterized in terms of mechanical properties, membrane drug uptake and drug release behavior, and application in transdermal delivery, demonstrating to have desirable mechanical properties and improved release of API-ILs. The assessment of anti-inflammatory activity through the inhibition of LPS-induced production of nitric oxide and prostaglandin E2 by macrophages revealed that the prepared membranes containing API-ILs are as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assay confirmed improved the viability and adhesion of fibroblasts on PVDF/HA membranes. Finally, wound healing assay performed with fibroblasts showed that the bilayer membranes containing dual-function API-ILs are not detrimental to wound healing, while displaying increased and controlled drug delivery and dual therapeutic behavior. Statement of significance This work shows the preparation and characterization of bilayer wound dressings comprising dual-biological function active pharmaceutical ingredients based on ionic liquids with improved and controlled drug release and dual therapeutic efficiency. By converting analgesic and anti-inflammatory drugs into ionic liquids, their water solubility increases up to 470-fold. The prepared bilayer wound dressing membranes have desirable mechanical properties and improved release of drugs. The prepared membranes comprising ionic liquids display anti-inflammatory activity as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assays show improved viability and adhesion of fibroblasts on PVDF/HA membranes, being thus of high relevance as effective transdermal drug delivery systems. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
publisher ELSEVIER SCI LTD
issn 1742-7061
isbn 1878-7568
year published 2019
volume 100
beginning page 142
ending page 157
digital object identifier (doi) 10.1016/j.actbio.2019.10.007
web of science category Engineering, Biomedical; Materials Science, Biomaterials
subject category Engineering; Materials Science
unique article identifier WOS:000501646900013
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  impact metrics
journal analysis (jcr 2019):
journal impact factor 7.242
5 year journal impact factor 7.502
category normalized journal impact factor percentile 89.769
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