A mild dosage form based on 5-Fluorouracil with AgNPs nanoparticles obtained by a modified "green" synthesis based on Grifola frondosa for the treatment of precancerous skin conditions

Precancerous skin diseases, including actinic keratosis, remain an urgent problem of dermatooncology due to the high prevalence and risk of malignancy. The use of 5-fluorouracil in the form of topical forms is limited by pronounced side effects and insufficient selectivity of action, which necessitates the development of new dosage forms with improved pharmacological characteristics. The aim of the study was to develop a mild dosage form based on 5-fluorouracil with silver nanoparticles obtained by modified "green" synthesis using Grifola frondosa extract and to evaluate its physico-chemical and biopharmaceutical properties. 5-fluorouracil, excipients (polyethylene glycols, glycerin, hydroxypropyl cellulose, etc.) and Grifola frondosa mushroom extract were used in the work. Silver nanoparticles were synthesized by the method of modified "green" synthesis using ascorbic acid. The study included spectrophotometric analysis, electron microscopy, determination of rheological characteristics, assessment of pH, uniformity of distribution, quantitative content of the active substance, as well as the study of stability and microbiological purity of the dosage form. It has been established that the obtained silver nanoparticles have a size of 220-250 nm and are characterized by stability. The developed mild dosage form has a homogeneous structure, optimal pH (6.8–7.2), pronounced thixotropic properties and satisfactory release rates of the active substance. It has been shown that the inclusion of silver nanoparticles and Grifola frondosa components contributes to the formation of a multilevel 5-fluorouracil delivery system, providing prolonged action and a potential reduction in toxicity. The compliance of the drug with the requirements of microbiological purity and stability has been established; the predicted shelf life is 24 months. As a result of the study, a new mild dosage form of 5-fluorouracil with silver nanoparticles obtained by the "green" synthesis method was developed and substantiated. The resulting drug is a promising delivery system with combined antitumor and antimicrobial effects, with improved technological and biopharmaceutical characteristics.