Preparation and Evaluation of Cubic Nanoparticles for Improved Transdermal Delivery of Propranolol Hydrochloride

Transdermal drug delivery of propranolol hydrochloride (PRH) is promising for the treatment of infantile hemangioma (IH). Clinically used PRH hydrogel fails to reach the deep IH for complete recovery. In this study, the PRH-loaded cubic nanoparticles (CNPs) were prepared to promote the transdermal effect of PRH. A remote drug loading method was developed to prepare the PRH-CNPs. For the traditional passive drug loading method, the largest encapsulation efficiency (EE%) was around 50%. The remote drug loading was performed by increasing the pH of the mixture of blank CNPs and PRH solution. The optimal PRH-CNPs showed an EE% of 90.15 ± 2.44% at pH 8.5. The permeation of the PRH solution was poor while the PRH-CNPs showed greatly enhanced skin permeation. It was found that smaller-sized PRH-CNPs contributed to increased skin permeation and retention. In addition, the PRH-CNPs had higher cytotoxicity towards the EOMA cells when compared with the PRH solution. During storage for 1 month, the PRH-CNPs kept stable size distribution, pH, and EE%. In conclusion, results of this study suggested that the PRH-CNPs could be a potential candidate for the treatment of the IH by transdermal delivery.