Venturi-based rapid expansion of supercritical solution (Vent-RESS): synthesis of liposomes for pH-triggered delivery of hydrophilic and lipophilic bioactives

Abstract

Multivitamin-loaded and surface-modified liposomes tailored for simultaneous intestinal delivery of both lipophilic and hydrophilic bioactives were synthesized from sunflower phosphatidylcholine (SFPC). Liposomes (SL) were generated with the aid of a novel, organic solvent free, and environmentally benign process which utilizes venturi-based rapid expansion of supercritical solution (Vent-RESS). Vitamins E and C were used as model lipophilic and hydrophilic bioactives and demonstrated an average encapsulation efficiency of 92 and 70%, respectively. Synthesized liposomes were coated with a pH-responsive double-wall of chitosan and β-lactoglobulin (βlg-Cs-SL) to develop a biocompatible vehicle for pH-triggered delivery of bioactive cargo(s). To compare the efficacy of this newly developed dual-coating, SL was also coated with a commercially available pH responsive polymer, Eudragit® S100 (Eu-SL). No organic solvent was used during the surface coating of SLs with these two different types of enteric coatings. The performance of these two coatings was studied by conducting morphological characterization through diameter and ζ-potential measurements along with confocal laser scanning and freeze-fracture cryogenic scanning electron microscopies. The stability of coated and uncoated SFPC liposomes was determined in simulated gastrointestinal fluids. For βlg-Cs-SL and Eu-SL, after 2 h of incubation in simulated gastric condition, less than 5% of the encapsulated vitamins C and E were released, whereas for SL, 41 and 28% of vitamins C and E were released within 2 h of incubation period. In simulated intestinal fluid, coated liposomes released most of their remaining payload when incubated for 4 h. The newly developed dual coating was found to be as effective as its commercially available counterpart, Eudragit® S100 coating; nevertheless, the biocompatible, non-toxic, and non-synthetic nature of this coating makes it an attractive alternative. Modeling the release kinetics of vitamins from coated liposome showed that the release of payload from surface coated liposomes proceeded through a multistep structural disintegration involving both Fickian and non-Fickian types of diffusion. The ability of these surface-coated liposomes to maintain structural integrity under the gastric condition followed by site-specific, pH-triggered release of encapsulated cargo in the intestine will make them highly suitable for oral administration of bioactive compounds in pharmaceutical and food applications.