Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.

Rivaroxaban (RXB), an oral direct factor Xa inhibitor, presents innovative therapeutic profile. However, RXB has shown adverse effects, mainly due to pharmacokinetic limitations, highlighting the importance of developing more effective formulations. Therefore, this work aims at the preparation, physicochemical characterization and in vitro evaluation of time-dependent anticoagulant activity and toxicology profile of RXB-loaded poly(lactic- co -glycolic acid) (PLGA)/poloxamer nanoparticles (RXBNps). RXBNp were produced by nanoprecipitation method and physicochemical characteristics were evaluated. In vitro analysis of time-dependent anticoagulant activity was performed by prothrombin time test and toxicological profile was assessed by hemolysis and MTT reduction assays. The developed RXBNp present spherical morphology with average diameter of 205.5 ± 16.95 nm (PdI 0.096 ± 0.04), negative zeta potential (−26.28 ± 0.77 mV), entrapment efficiency of 91.35 ± 2.40%, yield of 41.81 ± 1.68% and 3.72 ± 0.07% of drug loading. Drug release was characterized by an initial fast release followed by a sustained release with 28.34 ± 2.82% of RXB available in 72 h. RXBNp showed an expressive time-dependent anticoagulant activity in human and rat blood plasma and non-toxic profile. Based on the results presented, it is possible to consider that RXBNp may be able to assist in the development of promising new therapies for treatment of thrombotic disorders.

The skin plays a crucial role in the body's homeostasis through its thermoregulation functions, metabolic activity, and, mainly, its barrier function. Once this system has its homeostasis disturbed, through the promotion of tissue discontinuity, an injury happens and a restoration process starts. Different products can be used to promote, accelerate, or stimulate the healing process, such as hydrogels, emulsions, and ointments (main conventional formulations). Despite the historical use and wide market and consumer acceptance, new systems emerged for wound management with the main challenge to overcome conventional form limitations, in which nanosystems are found, mainly nanobased emulsion forms (nano- and microemulsions, NE and ME). Here, we discuss the skin function and wound healing process, highlighting the cellular and molecular processes, the different wound classifications, and factors that affect physiological healing. We also investigated the recent patents (2012-2023) filed at the United States Patent and Trademark Office, where we found few patents for conventional forms (hydrogels = 5; emulsions = 4; ointments = 6) but a larger number of patents for nanobased emulsions filed in this time (NE = 638; ME = 4,072). Furthermore, we address the use of nanobased emulsions (NE and ME) and their particularities, differences, and application in wound treatment. This work also discusses the challenges, bottlenecks, and regulatory framework for nanosystems, industrial, academic, and government interest in nanotechnology, and future perspectives about this key factor for the nanosystems market and consumer acceptance.

Background: Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. Current treatments are restricted to a small number of drugs that display both severe side effects and a potential for parasites to develop resistance. A new N-(3,4-methylenedioxyphenyl)-N'- (2-phenethyl) thiourea compound (thiourea 1) has shown promising in vitro activity against Leishmania amazonensis with an IC₅₀ of 54.14 μM for promastigotes and an IC₅₀ of 70 μM for amastigotes. Objective: To develop a formulation of thiourea 1 as an oral treatment for leishmaniasis, it was incorporated into nanoparticles (NPs), a proven approach to provide long-acting drug delivery systems Method: NPs of poly (D,L-lactic-co-glycolic acid) (PLGA) polymeric NPs containing thiourea 1 were obtained through a nanoprecipitation methodology associated with solvent evaporation. The NPs containing thiourea 1 were characterized for encapsulation efficiency (EE%), reaction yield (% w/w), surface charge, particle size and morphology by transmission electron microscopy (TEM). Results: NPs with thiourea 1 showed an improved in vitro leishmanicidal activity with a reduction in its cytotoxicity against macrophages (CC50>100 µg/mL) while preserving its IC50 against intracellular amastigotes (1.46 ± 0.09 µg/mL). This represents a parasite selectivity index (SI) of 68.49, which is a marked advancement from the reference drug pentamidine (SI = 30.14). Conclusion: The results suggest that the incorporation into NPs potentiated the therapeutic effect of thiourea 1, most likely by improving the selective delivery of the drug to the phagocytic cells that are targeted for infection by L. amazonensis. This work reinforces the importance of nanotechnology in the acquisition of new therapeutic alternatives for oral treatments.