Deep Eutectic Liquids as a Topical Vehicle for Tadalafil: Characterisation and Potential Wound Healing and Antimicrobial Activity

Abstract

Deep eutectic solvents (DESs) and ionic liquids (ILs) offer novel opportunities for several pharmaceutical applications. Their tunable properties offer control over their design and applications. Choline chloride (CC)-based DESs (referred to as Type III eutectics) offer superior advantages for various pharmaceutical and therapeutic applications. Here, CC-based DESs of tadalafil (TDF), a selective phosphodiesterase type 5 (PDE-5) enzyme inhibitor, were designed for implementation in wound healing. The adopted approach provides formulations for the topical application of TDF, hence avoiding systemic exposure. To this end, the DESs were chosen based on their suitability for topical application. Then, DES formulations of TDF were prepared, yielding a tremendous increase in the equilibrium solubility of TDF. Lidocaine (LDC) was included in the formulation with TDF to provide a local anaesthetic effect, forming F01. The addition of propylene glycol (PG) to the formulation was attempted to reduce the viscosity, forming F02. The formulations were fully characterised using NMR, FTIR and DCS techniques. According to the obtained characterisation results, the drugs were soluble in the DES with no detectable degradation. Our results demonstrated the utility of F01 in wound healing in vivo using cut wound and burn wound models. Significant retraction of the cut wound area was observed within three weeks of the application of F01 when compared with DES. Furthermore, the utilisation of F01 resulted in less scarring of the burn wounds than any other group including the positive control, thus rendering it a candidate formula for burn dressing formulations. We demonstrated that the slower healing process associated with F01 resulted in less scarring potential. Lastly, the antimicrobial activity of the DES formulations was demonstrated against a panel of fungi and bacterial strains, thus providing a unique wound healing process via simultaneous prevention of wound infection. In conclusion, this work presents the design and application of a topical vehicle for TDF with novel biomedical applications.