Mucoadhesive nanostructured systems comprising poloxamer 407 and Carbopol 974P^® have already demonstrated good mucoadhesion, as well as improved mechanical and rheological properties. Curcumin displays excellent biological activity, mainly in oral squamous cancer; however, its physicochemical characteristics hinder its application. Therefore, the aim of this study was to develop nanostructured formulations containing curcumin for oral cancer therapy. The photophysical interactions between curcumin and the formulations were elucidated by incorporation kinetics and location studies. They revealed that the drug was quickly incorporated and located in the hydrophobic portion of nanometer-sized polymeric micelles. Moreover, the systems displayed plastic behavior with rheopexy characteristics at 37 °C, viscoelastic properties and a gelation temperature of 36 °C, which ensures increased retention after application in the oral cavity. The mucoadhesion results confirmed the previous findings with the nanostructured systems showing a residence time of 20 min in porcine oral mucosa under flow system conditions. Curcumin was released after 8 h and could permeate through the porcine oral mucosa. Cytotoxicity testing revealed that the formulations were selective to cancer cells over healthy cells. Therefore, these systems could improve the physicochemical characteristics of curcumin by providing improved release and permeation, while selectivity targeting cancer cells.

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic^® and Carbopol^® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.

In this work, graphene quantum dots (GQDs) were synthesized from Moringa oleifera seed biomass doped with phosphorus, using a low-cost, renewable hydrothermal method. The biomass was ground and sieved (30 mesh), and the classified powder was transferred to a Teflon capsule, placed in a stainless-steel reactor (210 ºC, 24 h). Afterwards, 20 mL of distilled water were added to the synthesized GQDs, stirred for 30 min, and filtered through Whatman filter paper. Then they were centrifuged (12000 rpm, 10 min) and filtered through a 0.22 μm membrane. The filtrate was dialyzed in a cellulose dialysis bag, with a cut-off size of 3.5 kDa, for 7 days in absolute ethanol (99.5%), with gentle stirring, and the dialysate was exchanged every 24 h. The dialysate was dried at 105 ºC for 24 h. The GQDs were characterized by X-ray energy dispersive spectroscopy (EDX), Fourier-transform infrared spectroscopy (FTIR), UV-vis electronic absorption, fluorescence emission, X-ray Diffraction and high-resolution transmission electron microscopy (HRTEM). The results show the GQDs with an average size of 18.63 ± 4.24 nm and high fluorescence (bright blue) under ultraviolet light (365 nm). Our GQDs are promising for application in bioimaging and bioanalysis.

The native fruits of the Cerrado have an interesting composition of bioactive compounds responsible for antioxidant, anti-inflammatory, and antimicrobial activities, with technological potential for functional industries. This study investigated the extraction of bioactive compounds in cagaita and mamacadela fruits, under different conditions, using eutectic solvents based on choline chloride (CC) with citric acid (CA) or tartaric acid (TA), plus ethanol as reference. For a better understanding of the extracts, their antioxidant capacity was assessed by the DPPH^•, FRAP, ABTS^•+, and total phenolic compounds and flavonoids assays, as well as for color, water activity, and identification of bioactive compounds by mass spectrometry. Additionally, the carotenoid contents were evaluated in the ethanolic extracts. The results showed that ethanol was efficient for the extraction of flavonoids and presented advantages demonstrated in the antioxidant analyses of ABTS^•+ and FRAP. However, eutectic solvents stood out in the extraction of phenolic compounds, with yields 14.0 and 4.5 times higher than ethanol for mamacadela and cagaita, respectively. In addition, when compared to cagaita, mamacadela had twice the carotenoid content. Furthermore, the CC:TA solvent was the most efficient, demonstrating, by DI-ESI-MS, 29 phenolic compounds in mamacadela and 27 in cagaita. Therefore, the extracts obtained present potential for use as natural pigments, adding value to the fruits and encouraging their exploration by industries.

Bioactive peptides develop diverse functions and represent an underexplored biotechnological resource. Moringa oleifera Lam., due to its high protein content, is a promising raw material for generating these compounds. This study aimed to obtain di- and tripeptides-key molecules for rapid cellular absorption-by optimizing alkaline and enzymatic (Alcalase®) hydrolysis of dried M. oleifera leaves to maximize the release of small bioactive peptides. A full factorial response surface design was applied to evaluate two independent variables (M. oleifera mass and reagent concentration) and two response variables (protein content and degree of hydrolysis), using KOH, NaOH, and Alcalase®. The most promising hydrolysates were analyzed by liquid chromatography-tandem mass spectrometry for peptide identification, followed by DPPH assays to determine antioxidant activity and mineral analysis of the hydrolysis residues. A total of 66 dipeptides and 33 tripeptides were identified. Hydrolysis with 5% KOH and 21% M. oleifera yielded 4.54% total proteins, while the combination of 5% KOH and 11% Moringa produced the highest degree of hydrolysis (87.55%) and four tripeptides. Enzymatic hydrolysis with 10% Alcalase® and 11% M. oleifera resulted in a 63.41% degree of hydrolysis and the identification of 41 dipeptides and 10 tripeptides. These peptides demonstrated potential to inhibit ACE, dipeptidyl peptidase III and IV, renin, glycosidase, antioxidant action and the ability to chelate zinc, iron, and calcium. The solid residues generated during hydrolysis were rich in essential minerals. Application of the Alcalase® hydrolysate to Phaseolus vulgaris seedlings produced a 10% antioxidant response (compared to 0.19% in the control), supporting its potential as a biostimulant with antioxidant properties for vegetable crops.

Endophytic fungi are prolific sources of bioactive natural products, but many biosynthetic gene clusters remain silent under laboratory conditions. Following the OSMAC approach, the epigenetic modifiers nicotinamide and sodium butyrate (10 µM) were added to triplicate liquid cultures of Curvularia sp. G6‐32, an endophyte of Sapindus saponaria , and the crude extracts were analyzed by UHPLC‐MS/MS with Mzmine 3 processing and GNPS molecular networking. In total, 712 features were detected: 474 common to all treatments, 65 exclusive to the control, and 154 occurring only in the presence of the modifiers (7 nicotinamide, 9 sodium butyrate, 138 both). PCA, ANOVA ( p < 0.05) and volcano analysis (Student's t ‐test, p < 0.05, n = 3) separated the treated cultures from the control. Among 34 putatively identified compounds, diketopiperazines were the most abundant family (15 ionic species), whereas loliolide, γ‐linolenic acid and N‐(3‐hydroxytetradecanoyl)‐DL‐homoserine lactone illustrate the diversification elicited by both modifiers.