Abstract
Herpes simplex virus type 1 infection commonly affects many people, causing perioral sores, as well as severe complications including encephalitis in immunocompromised patients. The main pharmacological approach involves synthetic antiviral drugs, among which acyclovir is the golden standard, often leading to resistant virus strains under long-term use. An alternative approach based on antiviral plant-derived compounds, such as quercetin and mangiferin, demonstrated an antiviral potential. In the present study, semisolid forms for cutaneous application of quercetin and mangiferin were designed and evaluated to treat HSV-1 infection. Phosphatidylcholine- and poloxamer-based gels were produced and characterized. Gel physical–chemical aspects were evaluated by rheological measurements and X-ray diffraction, evidencing the different thermoresponsive behaviors and supramolecular organizations of semisolid forms. Quercetin and mangiferin diffusion kinetics were compared in vitro by a Franz cell system, demonstrating the different gel efficacies to restrain the polyphenol diffusion. The capability of gels to control polyphenol antioxidant potential and stability was evaluated, indicating a higher stability and antioxidant activity in the case of quercetin loaded in poloxamer-based gel. Furthermore, a plaque reduction assay, conducted to compare the virucidal effect of quercetin and mangiferin loaded in gels against the HSV-1 KOS strain, demonstrated the suitability of poloxamer-based gel to prolong the polyphenol activity.
Highlights
Three different formulations were evaluated: OG, an oleaginous gel based on PC and IPP, a hydrogel based on poloxamer 407 (P407) (POL) and a poloxamer organogel (POG), that can be considered as a hybrid form of OG and Poloxamer gel (POL)
The present study suggested the suitability of POL and POG as topical vehicles for polyphenols in the possible treatment or adjuvant therapy of HSV-1 infection
Both QT and MG were successfully loaded in P407- and PC-based gels, with a better ability of POL to solubilize QT and MG with respect to OG and POG
Summary
Pharmaceutical research has increasingly rediscovered the possibility of using plant-derived substances for therapeutic purposes instead of synthetic molecules, based on their more favorable potential in terms of safety and efficacy [1]. In this regard, natural molecules can be an efficacious alternative in case of drug resistance, resulting, for instance, in the treatment of some viral infections, such as that induced by HSV-1, whose handling has become challenging [2,3,4]. Immunosuppression can lead to the development of antiviral drug resistance, resulting
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