Impact of phospholipids, surfactants and cholesterol selection on the performance of transfersomes vesicles using medical nebulizers for pulmonary drug delivery

Abstract

The aim of this study is to formulate and optimize novel transfersome formulations for pulmonary drug delivery. Transfersome formulations (F1 – F18) were prepared by a thin-film method using three phospholipids (Soya phosphatidylcholine (SPC), Dimyristoly phosphatidylcholine (DMPC) and Hydrogenated soya phosphatidylcholine (HSPC)), in combination with three different surfactants (Tween 80, Span 80 and Span 20) with or without cholesterol, employing Beclomethasone dipropionate (BDP) as the model drug. Nano-transfersome formulations post-extrusion were delivered to a Two-stage Impinger (TSI) via three medical nebulizers (i.e. Air-jet, Ultrasonic and Vibrating mesh nebulizer). Based on the physicochemical properties, formulations F1 (SPC and Tween 80), F7 (DMPC and Tween 80) and F13 (HSPC and Tween 80) demonstrated significantly smaller VMD (162.34 ± 6.48, 198.66 ± 6.64, and 183.52 ± 7.34 nm), and significantly higher entrapment efficiency (97.56 ± 2.45, 95.67 ± 4.26 and 95.06 ± 3.38%). Based on nebulization performance, the Ultrasonic nebulizer exhibited the shortest nebulization time for formulations F1, F7 and F13 (i.e. 17.88 ± 2.45, 19.26 ± 2.04 and 19.59 ± 2.12 min), and higher output rate (212.04 ± 11.54, 194.61 ± 10.27 and 192.43 ± 9.84 mg/min), when compared to Air-jet and Vibrating mesh nebulizers. Irrespective of nebulizer type, significantly higher BDP deposition was observed in the lower stage of TSI for the F1 formulation (on average of 61%), whereas a higher amount of BDP was deposited in the upper stage of TSI using the F7 formulations (49%). Moreover, Formulation F1 in combination with Air-jet nebulizer demonstrated higher emitted dose (ED) and fine particle fraction (FPF) (82% and 83%), when compared to the counterpart formulations and nebulizer types investigated. This study has demonstrated that based on nebulizer performance, BDP deposition and formulation type; the F1 formulation in combination with an Air-jet nebulizer is most optimal for lower respiratory tract deposition, whereas the F7 formulation in combination with an Ultrasonic nebulizer is ideal for upper respiratory tract deposition.