In vitro applicability of mixed soy lecithin-based liposomes with added several lipophilic agents as novel delivery systems for delivery of quercetin

Abstract

The study used highly lipophilic compounds to evaluate membrane physical and constitutional changes and vesicle stabilization of mixed soy lecithin (ML)-based liposomes. The in vitro bio-accessibility of novel quercetin (QU)-loaded ML-based liposomes as a function of particle size, polydispersity index (PDI), zeta potential (ZP), different membrane stabilizers, membrane fluidity and encapsulation efficacy (EE) was examined. Three different membrane systems, empty ML-based liposomes (E-LPs), squalene (SQ) loaded LPs (SQ-LPs), and SQ and a combination of β-sitosterol (βS) and stigmasterol (ST) loaded LPs (SQ-βS-ST-LPs), were developed based on optimized formulations using an extrusion method and used to encapsulate QU. The applicability of the ML-based liposomal carriers was tested by means of an in-vitro digestion procedure by applying a 2-phase static in- vitro model of the stomach and small intestine allowing for measurement of the bio-accessibility of ingested QU. Stability comparison of the empty liposomal particles, SQ-LPs and SQ-βS-ST-LPs particles was carried out to determine the most appropriate form of QU-loaded ML-based liposomal formulation. Different formulations were observed to possess different amounts of bio-accessible QU, indicating that membrane additives had profound effect on micellization of QU during Gastro-Intestinal Tract (GIT). Bivariate correlation analysis indicated that the %bio-accessibility and %EE of QU were strongly linearly correlated (R² = 0.989), suggesting that QU bio-accessibility depended strongly on the retaining of QU in the ML bilayer, and entrapment capacity of the system. Our results paint a consistent picture in which the vesicle integrity, membrane fluidity and membrane-stabilizing function varied upon changing the membrane lipid composition in the ML-based-liposomes.

Graphical Abstract

Keywords:

• Bio-accessibility
• mixed liposome
• quercetin
• encapsulation efficacy
• differential scanning calorimetry

Authorship contribution statement

"S.P.T." has contributed to conceptualization, data curation, formal analysis, investigation and writing the manuscript. "T.B.T. has contributed to the supervision, visualization, writing - review & editing. “L.Z.C.” has contributed to the validation and writing - review & editing. "Y.L." has contributed to the visualization and writing - review & editing. "C.P.T." has contributed to the project administration, conceptualization, supervision, writing - review & editing.

Additional information

Funding

The authors would like to thank Ministry of Higher Education under the Fundamental Research Grant Scheme (FRGS) number: FRGS/1/2020/WAB04/UPM/01/4 for funding this project. Ministry of Higher Education, Malaysia.