A comprehensive production method of self-cryoprotected nano-liposome powders

Abstract

This study provided a convenient approach for large scale production of hydrogenated soya phosphatidylcholine nano-liposome powders using beclometasone dipropionate as a model drug and sucrose as proliposome carrier. Fluid-bed coating was employed to manufacture proliposomes by coating sucrose with the phospholipid (5%, 10%, 15% and 20% weight gains), followed by hydration, size reduction using high pressure homogenization, and freeze-drying to yield stable nano-vesicles. High pressure homogenization was compared with probe-sonication in terms of liposome size, zeta potential and drug entrapment. Furthermore, the effect of freeze-drying on vesicle properties generated using both size reduction methods was evaluated. Results have shown that high-pressure homogenization followed by freeze-drying and rehydration tended to yield liposomes smaller than the corresponding vesicles downsized via probe-sonication, and all size measurements were in the range of 72.64-152.50 nm, indicating that freeze-drying was appropriate, regardless of the size reduction technique. The liposomes, regardless of size reduction technique and freeze drying had slightly negative zeta potential values or were almost neutral in surface charge. The entrapment efficiency of BDP in homogenized liposomes was found to increase following freeze-drying, hence the drug entrapment efficiency values in rehydrated liposomes were 64.9%, 57%, 69.5% and 64.5% for 5%, 10%, 15% and 20% weight gains respectively. In this study, we have reported a reliable production method of nano-liposomes based on widely applicable industrial technologies such as fluid-bed coating, high pressure homogenization and freeze-drying. Moreover, sucrose played a dual role as a carrier in the proliposome formulations and as a cryoprotectant during freeze-drying.