Ketoconazole (KZ) is a broad-spectrum drug used to treat fungal infections. Local use of ketoconazole has been associated with some side effects in healthy adults, especially local reactions, such as stinging, severe irritation, and itching. Moreover, the bioavailability of KZ after oral administration is low in tablets due to its low water solubility. In addition, oral administration of ketoconazole produces systemic exposure, associated with significant side effects, such as cholestatic and hepatocellular lesions. In an attempt to reduce hepatotoxicity, ketoconazole may be administered at the primary site of infection with cutaneous candidiasis, specifically on the skin tissue. However, the use of ketoconazole in topical dosage forms is limited by its high lipophilicity and extremely poor aqueous solubility (1 ng/mL), thus leading to the rare availability of topical dosage forms on the market. Therefore, a new approach to the effective delivery of ketoconazole to the site of infection is targeted, including obtaining new derivatives (keeping the imidazolic nucleus), with a similar spectrum of action, and finally, their inclusion in betacyclodextrin complexes in order to optimize bioavailability and physico-chemical stability.

Quercetin is one of the most abundant plant flavonoids and an intensively studied bioactive compound belonging to the class of functional heterocyclic compounds with outstanding biological activities, due to its numerous biological, pharmacological and therapeutic effects. This paper presents the main information on the chemical structure, dietary sources, absorption, metabolism and bioavailability of quercetin, highlighting the role of the intestinal microbiota in the formation of metabolites responsible for an important part of its effects. The limitations related to stability and bioavailability are analyzed as well as modern formulation strategies and advanced delivery systems aimed at improving the efficacy of the compound. The major biological activities of quercetin are also summarized, including antioxidant, anti-inflammatory, immunomodulatory, antiviral, cardioprotective, neuroprotective, metabolic and anticancer effects. Unlike previous reviews, which have generally addressed these topics separately, the present work integrates the gut-microbiota-mediated metabolism, cellular senescence, advanced delivery systems, combined therapies, and safety and regulatory considerations within a unified translational framework. Overall, this review emphasizes the need to relate the multifunctional biological potential of quercetin to its pharmacokinetic limitations, formulation performance and clinically achievable exposure while highlighting the need for standardized formulations and further clinical studies to validate its therapeutic benefits.