Development and characterization of nanostructured lipid carriers containing propranolol hydrochloride for treatment of infantile hemangioma
Propranolol; infantile hemangioma; nanostructured lipidic carriers; box-behnken design
Infantile hemangioma (hi) is classified as a benign tumor of endothelial cells and affects a considerable portion of the infant population. Its manifestation can occur in a mild or more advanced form and, depending on the classification of the pathology, propranolol hydrochloride, the first-choice treatment, should be used to assist in the remission of hi. However, the systemic therapy used in pediatric patients can trigger several adverse effects in them, thus envisioning the need to develop topical formulations with this drug to reduce or even end these unpleasant effects. In view of the above problem, the present work is justified by the demand for new technologies for the management of hi that do not present unwanted effects in pediatric patients. Therefore, a development of nanostructured lipid carriers (ncl) with different sizes was proposed through a box-behnken predictive model using the microemulsion technique. The compatibility between the inputs involved in the production process was studied through the application of thermochemical analysis associated with centroid simplex experimental design. The nlcs were characterized in terms of average size, polydispersity index (pdi), zeta potency and encapsulation efficiency (ee). The performance of nanodispersions was evaluated according to release kinetics and permeation profile in vitro and in vitro studies in hbmec cells were conducted to evaluate the inhibitory potential of hi. As a result, nlcs of 500 and 900nm were obtained, with acceptable pdi given the difficulty in obtaining this type of formulation with low levels of polydispersion, and ee greater than 99.0%. The two formulations obtained controlled the release of ppl in 24 hours and its accumulation in the target tissue for topical therapy of hi. In addition, positive results of inhibition of cell proliferation were observed.