A Long-Lasting Skin Protectant Based on CG-101, a Deep Eutectic Solvent Comprising Choline and Geranic Acid.

The COVID-19 public health crisis has spotlighted the need to improve global hygiene and sanitization. In addition to causing staggering rates of transmission and fatality, COVID-19 has severely impacted the quality of life and mental health of global citizens. The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) encourage hand hygiene as the first defense against the spread of infection, yet frequent handwashing is often impractical. Widely used ethanol-based hand sanitizers provide immediate protection against pathogens on the skin, albeit short-lived, due to their rapid evaporation. Herein, a novel, long-lasting skin protectant formulated with biocompatible ionic liquid/deep eutectic solvents prepared using generally recognized as safe materials - choline and geranic acid (CG-101, 5% w/w) - is described. In vitro studies demonstrated that CG-101 inactivates bacteria and the human coronavirus, hCoV229E, for 4 h after application. Two human clinical studies demonstrate that CG-101 does not cause skin irritation or sensitization, and a single application of CG-101 gel imparts skin protection against microbes for significantly longer than conventional 70% ethanol-based hand sanitizers. These data are the first to indicate that CG-101 may be a better alternative to alcohol-based hand sanitizers for long-term skin protection against infectious diseases.

Clinical translation of choline and geranic acid deep eutectic solvent.

Choline geranate deep eutectic solvent/ionic liquid (CAGE) has shown several desirable therapeutic properties including antimicrobial activity and ability to deliver drugs transdermally in research laboratories. Here, we describe the first report of clinical translation of CAGE from the lab into the clinic for the treatment of rosacea, a common chronic inflammatory skin disorder that affects the face. We describe the seven steps of clinical translation including (a) scale-up, (b) characterization, (c) stability analysis, (d) mechanism of action, (e) dose determination, (f) GLP toxicity study, and (g) human clinical study. We describe the challenges and outcomes in these steps, especially those that uniquely arise from the deep eutectic nature of CAGE. Our translational efforts led to a 12-week open-label phase 1b cosmetic study with CAGE1:2 gel (CGB400) in mild-moderate facial rosacea in 26 patients where CGB400 exhibited a marked reduction in the number of inflammatory lesions. These results demonstrate the therapeutic potential of CGB400 for treating rosacea as well as it provides insights into the translational journey of deep eutectic solvents, in particular CAGE, for dermatological applications.

Enhanced percutaneous permeability of diclofenac using a new U-type dilutable microemulsion.

Enhanced systemic absorption in vivo and percutaneous penetration in vitro was demonstrated after transdermal administration of diclofenac sodium formulated in U-type microemulsion. Diclofenac sodium was solubilized in a typical four-component system consisting of an oil, polyoxyethylene-10EO-oleyl alcohol (Brij 96V) as the surfactant, and 1-hexanol along water dilution line W46 (40 wt % surfactant and 60 wt % oil phase before water titration). Viscosity and small angle X-ray scattering measurements have evidenced bicontinuous structures within water fractions of 0.25 and 0.5 along the dilution line. Self-diffusion NMR studies showed that drug molecules accumulated in the interfacial film and, to some extent, dissolved in the oil. Relative to a commercial macro-emulsion cream (Voltaren Emulgel), microemulsions containing paraffin oil or isopropyl myristate increased the in vivo transdermal penetration rate of diclofenac by two order of magnitude, whereas the rat plasma levels were increased by one order of magnitude. The in vitro data obtained from excised rat skin were comparable to the in vivo results, but suffered from discrepancies from the ideal in vivo-in vitro correlation, which might be explained by optimal in vitro conditions of perfusion and hydration. It has also been found that when jojoba oil is formulated as the oil phase in the microemulsion, the penetration rate of the drug decreases significantly. Based on the three-dimensional structure of jojoba oil, the wax is presumed to prevent the drug from being freely diffused into the skin while migrating from the interfacial film into the continuous oil phase.