Abstract

Drug delivery via aerosolization is a non-invasive and ideal method for targeting the pulmonary system, achieving localized effect. This study aims to formulate and compare five different types of lipid-based powder formulations: pro-micelles (F1-F3), pro-niosomes (F4-F6), pro-liposomes (F7-F9), pro-transfersomes (F10-F12), and pro-nanostructured lipid carriers (F13-F15), using three different lipid-to-sucrose carrier ratios (1:05, 1:10, and 1:15 w/w) via a slurry method, using a model anticancer drug, trans-resveratrol (TRES). Aerosolization performance was determined via a two-stage impinger (TSI) paired with two medical nebulizers (i.e., air-jet and vibrating mesh). Post-hydration, vesicles from pro-niosome formulations (F3-F6) demonstrated significantly larger particle size (>1200 nm), while from pro-transfersomes (F11-F13) showed smaller particle size (<125 nm). Entrapment efficiency for all formulations exceeded 90%. An elevated dynamic viscosity was recorded for all formulations when employing a type B Ostwald viscometer as opposed to A, C and D, regardless of formulation type. Upon nebulization, the vibrating mesh nebulizer was associated with an extended nebulization time (23-32 min), short sputtering time (1.57-5.59) and high mass output (79-95%) in compared to air-jet nebulizer (irrespective of formulation type). Both nebulization time and mass output increased significantly with increasing sucrose concentration in formulations (from 1:5 to 1:15 w/w ratio). Upon aerosolization performance, the vibrating mesh showed a significantly higher emitted dose (ED; 72-98%) and fine particle fraction (FPF; 60-81%) than its counterpart nebulizer. The in-vitro release profile depicted zero-order controlled drug release. Moreover, over a period of 24 h, the maximum release of TRES was found at pH 5, rather than at pH 7. Thus, it was concluded that formulations with a higher viscosity (with increasing sucrose concentration) and a vibrating mesh nebulizer are the best combination for peripheral drug deposition.