Development of Lecithin/Chitosan Nanoparticles for Promoting Topical Delivery of Propranolol Hydrochloride: Design, Optimization and In-Vivo Evaluation

Abstract

Propranolol (PPL) administered orally is considered as the first line drug for the treatment of infantile hemangioma, however several systemic adverse effects limit its use. For this reason, our work tackles the development and evaluation of PPL loaded chitosan nanoparticles (NPs), as an effective alternative for the treatment of infantile hemangioma. PPL -NPs were prepared using the double emulsion technique and the influence of the formulation variables on drug entrapment efficiency (EE), particle size (PS), percent released after 24 h (%R_24h) and zeta potential (ZP) were optimized using full factorial design. Two systems, namely F3 and F28 showing highest E.E., ZP and %R_24h with lowest PS, were fully characterized for DSC and TEM and incorporated into hydrogel with adequate viscosity. After ensuring safety for the selected nanoparticle, the hydrogel containing the optimized system was applied topically to rats. The in-vivo skin deposition in rats showed an accumulation of propranolol from the lecithin/chitosan nanocarrier by 1.56–1.91-fold when compared to the drug solution. The obtained result was further supported by the confocal laser scanning microscopy which showed fluorescence across the skin. PPL-HCL-loaded lecithin/chitosan nanoparticles could be considered as a potential candidate for treating infantile hemangiomas (IH) by maintaining therapeutic concentration topically while minimizing systemic side effects.