Two-Stage Supramolecular Self-Assembly-Directed Collagen-Peptide-Decorated Liposomal Complexes of Curcumin Microspheres with Enhanced Solubility and Bioavailability

[Image: see text] Green formulations of phytonutrients with enhanced solubility and bioavailability are of great significance in nutrition therapy. In the present contribution, we hypothesized that the collagen peptides could be a safe, natural, food-grade, and cost-effective functional agent for the surface decoration and stabilization of liposomes in powder form and hence a “green” solution for the oral delivery of phytonutrients. The present study reports a two-stage supramolecular self-assembly-directed process for the preparation of collagen peptide-decorated liposomal complexes of curcumin (CCL) [10% (w/w)] as microspheres (125 ± 25 μm) with improved solubility (1.46 × 10(5)-fold) and sustained-release properties under gastrointestinal pH conditions. The molecular self-assembly of collagen peptides around the lipid bilayers and the various noncovalent interactions and conformational changes leading to the supramolecular assembly to act as a matrix for the encapsulation of lipid vesicles of curcumin were clear from the spectroscopic studies (UV–vis, fluorescence, FTIR, and circular dichroism). Further investigation of pharmacokinetics following a randomized double-blinded controlled trial on healthy volunteers (n = 15) demonstrated that the oral administration of 2.5 g of CCL sachet (250 mg of curcumin) enhanced the plasma concentration (C(max): 118 vs. 4.3 ng/mL), the elimination half-life (4.2 vs. 0.7 h), and bioavailability as per the area under the curve over 12 h [AUC(0–12h) (CCL) = 506·8 vs. AUC(0–12h) (C95) = 9.47 (53-fold)], when the plasma concentration of curcumin was estimated with triple quadruple tandem mass spectrometry (UPLC-ESI-MS/MS).