Development and characterization of a nanoemulsion containing propranolol for topical delivery

Tatiana Zanela da Silva Marques,1 Ralph Santos-Oliveira,2 Luciana Betzler de Oliveira de Siqueira,1 Verônica da Silva Cardoso,3 Zaida Maria Faria de Freitas,1 Rita de Cássia da Silva Ascenção Barros,1 Ana Lúcia Vazquez Villa,1 Mariana Sato de Souza de Bustamante Monteiro,1 Elisabete Pereira dos Santos,1 Eduardo Ricci-Junior1 1Department of Drugs and Medicines, Faculty of Pharmacy, 2Institute of Nuclear Energy, 3Unit of Biocatalysis, Bioproducts and Bioenergy (Bioinivar), Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil Background: Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo.Methods: The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m.Results: NE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of −20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay.Conclusion: We concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas. Keywords: infantile hemangiomas, nanoemulsion, propranolol, ex vivo permeation studies, cytotoxicit

Estilos de vida na adolescência: comportamento sexual dos adolescentes portugueses

Estudos recentes têm demonstrado que actualmente os adolescentes iniciam a vida sexual cada vez mais cedo, sem contudo possuírem uma educação sexual consistente. Os objectivos deste estudo foram analisar o comportamento sexual de adolescentes do ensino secundário e identificar os hábitos de vigilância de saúde sexual em adolescentes, do ensino secundário, sexualmente activos. Realizou-se um estudo exploratório em que participaram 680 adolescentes, com idades entre 15 e 19 anos. Os resultados evidenciam que a maioria dos inquiridos ainda não iniciou a actividade sexual; são os rapazes os que mais reportam já ter tido relações sexuais; o preservativo não é um método utilizado por todos os adolescentes nas suas relações sexuais; a maioria dos adolescentes não faz vigilância de saúde sexual. É importante que os adolescentes sexualmente activos recebam cuidados de saúde e aconselhamento. As instituições de saúde e os seus profissionais necessitam de ser pró-activos tentando captar os adolescentes