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.