Propranolol-loaded nanostructured lipid carriers for topical treatment of infantile hemangioma

Abstract

Oral administration of propranolol hydrochloride (PPL) is a first-line treatment option for infantile hemangioma. However, systemic drug distribution has been associated with severe adverse effects. Thus, this study aimed to investigate the feasibility of using PPL-loaded nanostructured lipid carriers (NLC) for topical drug delivery as a safer alternative for hemangioma treatment. Rosa rubiginosa essential oil was selected as a liquid lipid and possible therapeutic adjuvant. NLC with two different diameters (500 and 900 nm) were prepared and evaluated regarding stability, drug release, skin permeation, and cell activity. The NLC exhibited diameters within the confidence interval of the predictive model (569 ± 87 nm and 824 ± 58 nm), polydispersity index of 0.5, zeta potential close to neutrality, pH 5.5, and entrapment efficiency of 99%. The NLC were stable under refrigeration and controlled PPL release for 12 h, following first-order and Weibull kinetics (coefficient of determination >0.95). In the permeation assays with intact skin, the NLC exhibited a lower drug accumulation in the deeper skin layers, at least 5-fold less than the drug solution, with 19.5 and 12.7 μg cm−2 for the NLC of 500 nm and 900 nm, respectively, versus 88.1 μg cm−2 for the PPL solution. Moreover, no PPL was found from the NLC in the receptor medium the PPL solution resulted in skin permeation of up to 43.4 ± 5.9 μg cm−2. Furthermore, this trend was maintained even when the formulations were applied to a skin model in which hair follicles were blocked. Lastly, PPL-loaded NLC exhibited significant toxic, anti-proliferative, and anti-migratory effects over human brain microvascular endothelial cells superior to the non-formulated drug. In fact, PPL-loaded NLC inhibited cell proliferation by ≥ 50% after 6 days and limited cell migration to approximately 25%, compared to approximately 100% of controls. Thus, topical PPL-loaded NLC proved to be a promising drug delivery system for the topical treatment of infantile hemangioma.