The largest organ of the body provides the main challenge for the transdermal delivery of lipophilic or high molecular weight drugs. To cross the main barrier of the skin, the stratum corneum, many techniques have been developed and improved. In the last 20 years, the association of microneedles with nanostructured systems has gained prominence for its versatility and for enabling targeted drug delivery. Currently, the combination of these mechanisms is pointed to as an emerging technology; however, some gaps need to be answered to transcend the development of these devices from the laboratory scale to the pharmaceutical market. It is known that the lack of regulatory guidelines for quality control is a hindrance to market conquest. In this context, this study undertakes a scoping review of original papers concerning methods applied to evaluate both the quality and drug/protein delivery of dissolving and hydrogel-forming microneedles developed in association with nanostructured systems.

Sesquiterpene compounds are applied as permeation promoters in topical formulations. However, studies exploring their impact on nanostructured systems, changes in permeation profile, and consequently, its biological activity are restricted. This study aimed to investigate the correlation between the skin permeation of the major sesquiterpenes, beta-caryophyllene, and caryophyllene oxide from the oleoresin of Copaifera multijuga, after delivery into topical nanoemulgels, and the in vivo antiedematogenic activity. First, ten nanoemulgels were prepared and characterized, and their in vitro permeation profile and in vivo anti-inflammatory activity were evaluated. In equivalent concentrations, β-caryophyllene permeation was greater from oleoresin nanoemulgels, resulting in greater in vivo antiedematogenic activity. However, an inverse relationship was observed for caryophyllene oxide, which showed its favored permeation and better in vivo anti-inflammatory effect carried as an isolated compound in the nanoemulgels. These results suggest that the presence of similar compounds may interfere with the permeation profile when comparing the profiles of the compounds alone or when presented in oleoresin. Furthermore, the correlation results between the permeation profile and in vivo antiedematogenic activity corroborate the establishment of beta-caryophyllene as an essential compound for this pharmacological activity of C. multijuga oleoresin.

Brunfelsia uniflora (Pohl) D. Don roots have been widely used in folk medicine for treating inflammatory conditions. However, few studies have elucidated compounds that justify their traditional use. This study was conducted to characterize the phytochemical profile and evaluate the in vitro antioxidant capacity, and in vivo anti-inflammatory activity of extracts obtained from B. uniflora roots by comparing an herbal remedy (HR) with the crude hydroalcoholic extract (CHE). In the phytochemical analysis, scopoletin was identified as the marker compound. In quantitative analyses, CHE showed better results than HR. Furthermore, CHE had an effective anti-inflammatory activity. Animals treated with CHE (200 mg/kg) showed an 89.1% and a 73.8% reduction in edema volume after 1 hour of edema induction compared with those treated with negative control and positive control (indomethacin), respectively. These results show that B. uniflora root extracts have promising antioxidant and anti-inflammatory activities, thus corroborating their application in ethnomedicine. Graphical Abstract

Cissus verticillata and Sphagneticola trilobata have been used in Brazilian folk medicine for Diabetes Mellitus treatment, although their pharmacological and toxicological profile has not been clearly established. Thus, the aim of this study was to evaluate the preclinical toxicity of the aqueous extracts of C. verticillata and S. trilobata. The main groups of secondary metabolites were investigated, and the species differed by the presence of coumarins in C. verticillata and by tannins in S. trilobata extracts. The highest contents of phenolic compounds and flavonoids were quantified in C. verticillata infusion with 2.594 ± 0.04 mg equivalents of gallic acid g-1 of extract and 1.301 ± 0.015 mg equivalents of catechin g-1 of extract, respectively. While the extract of S. trilobata showed minimum values of these compounds, with 0.002 ± 0.001 mg equivalents of gallic acid g-1 extract and 0.005 ± 0.0004 mg equivalents of catechin g-1 of extract, respectively. These differences implied the results of in vitro antioxidant activity evaluated using ferric reducing antioxidant power (FRAP), in which the sample of C. verticillata at 5 mg mL-1 showed a value of 122 µM ferrous sulfate equivalents (FSE), while S. trilobata showed 0.93 µM FSE at the same concentration. With respect to cytotoxic assay with murine fibroblast cell line (3T3) only S. trilobata exhibited cytotoxic effects measured by MTT and Sulforhodamine B assays, evidenced by the cell viability value of approximately 16%, in both tests after 24 and 72 hours of exposure of the cells to 5 mg mL-1 of the extract. Comparatively, at 5 mg mL-1 the C. verticillata extract showed cell viability of 142% and 95%, respectively, after 24 hours of cell exposure. On the other hand, both species showed genotoxic profiles evidenced by chromosomal aberrations by Allium cepa bioassay, observed by the higher percentage values of chromosome bridges, chromosome loss, and disturbed anaphase for all concentrations of both extracts than those of the negative control. The results support the characterization of the toxicological profile for both species and create an alert regarding the use of S. trilobata, which should be avoided.