Development and Characterization of Self-Assembling Sirolimus-Loaded Micelles as a Sublingual Delivery System

Abstract

The aim of this study was to develop self-assembling micelles of poorly water soluble potent immunosuppressant agent sirolimus (SRL) to enhance the solubility and mucosal permeability as stable aqueous formulations for sublingual administration. D-alpha-tocopheryl 1000 succinate (TPGS), soy phosphatidylcholine (SPC), and sodium cholate (NaC) were used to prepare the SRL-loaded micelles using the one-step self-assembly method. The mean hydrodynamic diameter of optimal micelles ranged from approximately 13 to 42 nm with low polydispersity index (PDI). The formulations possessed drug loading (DL) and drug encapsulation efficiency (EE) of around 18% and 99%, respectively. SPC caused an increase in mean hydrodynamic diameter and PDI of micelles, but no negative impact on DL and EE values was observed when used at concentrations of <= 25% (w/w) of amphiphiles. However, NaC caused a detrimental effect on the characteristics of micelles in every respect. Ex vivo permeation studies revealed that TPGS-based micelles without SPC were not able to enhance the permeation of SRL compared to the SRL solution through bovine sublingual mucosa. However, the incorporation of SPC into the micelles significantly increased the mucosal permeation of SRL compared to the SRL solution. The optimal formulations maintained their characteristics at 4 degrees C for at least 90 days. These results support the feasibility of SRL-loaded micelles as a sublingual delivery system.