Ibrutinib topical delivery for melanoma treatment: The effect of nanostructured lipid carriers' composition on the controlled drug skin deposition.

Melanoma is responsible for more than 80% of deaths related to skin diseases. Ibrutinib (IBR), a Bruton's tyrosine kinase inhibitor, has been proposed to treat this type of tumor. However, its low solubility, extensive first-pass effect, and severe adverse reactions with systemic administration affect therapeutic success. This study proposes developing and comparing the performance of two compositions of nanostructured lipid carriers (NLCs) to load IBR for the topical management of melanomas in their early stages. Initially, the effectiveness of IBR on melanoma proliferation was evaluated in vitro, and the results confirmed that the drug reduces the viability of human melanoma cells by inducing apoptosis at a dose that does not compromise dermal cells. Preformulation tests were then conducted to characterize the physical compatibility between the drug and the selected components used in NLCs preparation. Sequentially, two lipid compositions were used to develop the NLCs. Formulations were then characterized and subjected to in vitro release and permeation tests on porcine skin. The NLCs containing oleic acid effectively controlled IBR release over 24 h compared to the NLCs composed of pomegranate seed oil. Furthermore, the nanoparticles acted as permeation enhancers, increasing the fluidity of the lipids in the stratum corneum, as determined by EPR spectroscopy, which stimulated the IBR penetration more profoundly into the skin. However, the NLCs composition also influenced the permeation promotion factor. Thus, these findings emphasize the importance of the composition of NLCs in controlling and increasing the skin penetration of IBR and pave the way for future advances in melanoma therapy.

Alterations in innate immune responses of patients with chronic rhinosinusitis related to cystic fibrosis.

The role of phagocytes of children with cystic fibrosis (CF) associated with different phenotypes of chronic rhinosinusitis (CRS) is unclear. The aim of this study was to evaluate the phagocytic capacity of blood neutrophils and monocytes and production of superoxide anion by phagocytes in patients with CF with or without chronic rhinosinusitis and with or without nasal polyps (NP). This cross-sectional study was established in 2015-2017 in a tertiary reference center to the CF treatment, Brasilia, Brazil. Sample included 30 children volunteers with CRS related to CF (n = 16) and control subjects (n = 14). Epidemiological and clinical data were compared. Collection of 15 mL of peripheral blood and nasal endoscopy to identify the presence or absence of nasal polyps (NP) were performed. Phagocytosis of Saccharomyces cerevisiae by pathogen-associated molecular pattern receptors and opsonin receptors was assessed. Superoxide anion production was evaluated. The control group showed a higher phagocytic index to monocytes and neutrophils than to the CF or CF+CRS with NP groups [Kruskal-Wallis p = 0.0025] when phagocytosis were evaluated by pathogen-associated molecular pattern receptors (5 yeasts/cell). The phagocytic index of the CF+CRS without NP group was higher than in the CF+CRS with NP group (Kruskal-Wallis p = 0.0168). In the control group, the percentage of phagocytes involved in phagocytosis and superoxide anion production (74.0 ± 9.6%) were higher in all CF groups (p < 0,0001). The innate immune response, represented by phagocytic activity and superoxide anion production by monocytes and neutrophils was more impaired in patients with CF related or not related to CRS than in the control group. However, the phagocytic function of patients without NP showed less impairment.