Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.

Fungal infections are diseases that are considered neglected although their infection rates have increased worldwide in the last decades. Thus, since the antifungal arsenal is restricted and many strains have shown resistance, new therapeutic alternatives are necessary. Nanoparticles are considered important alternatives to promote drug delivery. In this sense, the objective of the present study was to evaluate the contributions of newly developed nanoparticles to the treatment of fungal infections. Studies have shown that nanoparticles generally improve the biopharmaceutical and pharmacokinetic characteristics of antifungals, which is reflected in a greater pharmacodynamic potential and lower toxicity, as well as the possibility of prolonged action. It also offers the proposition of new routes of administration. Nanotechnology is known to contribute to a new drug delivery system, not only for the control of infectious diseases but for various other diseases as well. In recent years, several studies have emphasized its application in infectious diseases, presenting better alternatives for the treatment of fungal infections.

The development of biodegradable nanoparticles is an important tool for the biological transport of chemical compounds. The nanoencapsulation reduces the biopharmaceutical and pharmacokinetic drawbacks of compounds and enhances their biological properties. Naturally occurring polymers such as proteins and polysaccharides have been widely applied in the development of nanostructured systems of several therapeutic agents. Among them is chitosan, a crustacean-carapace-chitin derived biopolymer. In addition to its biocompatibility and biodegradability, chitosan is known for its mucoadhesion properties. Chitosan-based nanostructured systems potentiate most of the aspects of the loaded drugs, including cellular transport and other biological effects. The use of chitosan nanoparticles enhances permeation, stability, and bioactivity of natural compounds. In this review, an overview of the main features of chitosan nanoparticles that improved in vitro and in vivo effects of bioactive natural molecules is given, emphasizing the results obtained with curcumin.

Tamoxifen (TAM) and curcumin (CUR) are compounds investigated for cancer treatment; however, tamoxifen is associated with side effects, especially reducing red blood cells, and curcumin has low bioavailability. Therefore, combining these compounds in an encapsulation system represents a promising therapeutic strategy. Poly-lactic acid nanoparticles (PLA-NPs) containing CUR, TAM, and their combination (CUR-TAM) were prepared via emulsification-solvent evaporation. The encapsulation efficiency was similar for both CUR and TAM, whether encapsulated individually or together, with approximately 57% for TAM and 92% for CUR. The nanoparticles exhibited spherical morphology, with an average size of approximately 200 nm. Zeta potential values were -16 mV for TAM, -26 mV for CUR, and -17 mV for CUR-TAM. In vitro release studies over 120 hours revealed 57% release for CUR and 49% for TAM in the CUR-TAM NPs. Hemolysis testing at 96 hours showed low hemolytic activity for all NPs while the antiproliferative activity against B16-F10 cells demonstrated a significant reduction in cell viability with CUR-TAM NPs (23%), compared to 89% for TAM NPs and 41% for CUR NPs. Combining CUR and TAM in nanoparticles is promising, offering potential therapeutic benefits while minimizing adverse effects.