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.
keywords
VITRO SKIN PERMEATION; SURFACE MODIFICATION; ANTIBACTERIAL ACTIVITY; POTENTIAL APPLICATION; THERMAL-STABILITY; CROSS-LINKING; PVDF MEMBRANE; HYDROGELS; SODIUM; NANOPARTICLES
subject category
Engineering; Materials Science
authors
Abednejad, A; Ghaee, A; Morais, ES; Sharma, M; Neves, BM; Freire, MG; Nourmohammadi, J; Mehrizi, AA
our authors
Groups
G4 - Renewable Materials and Circular Economy
G5 - Biomimetic, Biological and Living Materials
Projects
CICECO - Aveiro Institute of Materials (UID/CTM/50011/2019)
Igy Technology: A Purication Platform using Ionic-Liquid-Based Aqueous Biphasic Systems (IGYPURTECH)
acknowledgements
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, FCT Ref. UID/CTM/50011/2019, financed by national funds through the FCT/MCTES. The authors acknowledge the financial support from the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No. 739572 -The Discoveries CTR. M.G. Freire acknowledges the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 337753.