The poor oral bioavailability, rapid biotransformation to less active metabolites, and fast elimination from systemic circulation have been identified as the major limitations responsible for the clinical insignificance of many drug candidates and phytonutrients. Despite the technological advancements in the nanoformulations of synthetic drugs, there exist many challenges for nutritional therapy, due to the regulatory issues, use of high levels of synthetic emulsifiers and polymers, low stability, low loading levels, mainly liquid state, etc. Herein, we report the characterization and human pharmacokinetics of a natural self-emulsifying hybrid-hydrogel formulation of trans -resveratrol prepared by uniformly impregnating resveratrol micelles into the fenugreek galactomannan hydrogel scaffold to form a water-soluble micelle/hydrogel composite in powder form (RF-20). Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), particle size analysis by dynamic light scattering (DLS), and transmission electron microscopy (TEM) demonstrated the uniform impregnation of resveratrol micelles within the galactomannan hydrogel matrix to form a soluble (average particle size of 172.0 ± 10.4 nm and −21.0 ± 2.5 mV zeta potential) and amorphous powder form with smooth and translucent surface morphology for RF-20, with no chemical alterations. Upon pharmacokinetic studies on healthy human subjects ( n = 16) following a randomized, double-blinded, placebo-controlled, 2-arm, 4-sequence crossover design and tandem mass spectrometry (UPLC-ESI-MS/MS), 80 mg of trans -resveratrol from RF-20 provided enhanced free resveratrol bioavailability and pharmacokinetic properties compared to the unformulated resveratrol with 98% purity. The enhancement in bioavailability was more when supplemented in sachet (12.98-fold) form than the capsule (10.48-fold) with improved absorption ( C max = 50.97 ± 15.82 ng/mL), circulation half-life ( t 1/2 = 7.01 ± 1.44 h), and sustained delivery ( T max = 4.71 ± 0.73 h), as compared to the unformulated form ( C max = 15.07 ± 5.10 ng/mL; t 1/2 = 1.58 ± 0.65 h; T max = 1.21 ± 0.42 h).

A green process to modulate the surface properties of liposome was reported using fenugreek galactomannan hydrogel and successfully applied to vitamin C with significant enhancement in human oral bioavailability.

Despite the vast array of health beneficial pharmacological effects, the bioavailability of the dietary flavonoid quercetin was found to be poor due to insolubility, incompatibility, and rapid biotransformation. Herein, we investigated the solubility, morphology, particle size, stability, in vitro release, and human pharmacokinetics of a hybrid-hydrogel formulation of quercetin (FQ-35) using fenugreek galactomannans as the hydrogel scaffold. Physicochemical characterization revealed that the crystalline quercetin was well encapsulated in the hydrogel matrix to form translucent microgel particles of FQ-35 with enhanced solubility (96-fold). The mean particle size was found to be 183.6 ± 42.7 nm with a zeta potential of 35.1 ± 3.8 mV. Pharmacokinetic investigation on healthy volunteers (N = 16) employing tandem mass spectrometric (ultra-performance liquid chromatography-electrospray tandem mass spectrometry) measurements of the concentration of free (unconjugated) and conjugated quercetin metabolites revealed an 18.6-fold improvement in free (unconjugated) quercetin bioavailability and 62-fold improvement in total quercetin (sum of free and conjugated) bioavailability, compared to the unformulated quercetin extracted from Sophora japonica. In summary, the natural self-emulsifying reversible hybrid-hydrogel delivery system was found to offer significant solubility, stability, and bioavailability of quercetin upon single-dose oral administration.

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 costeffective 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 selfassembly 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 (53fold)], when the plasma concentration of curcumin was estimated with triple quadruple tandem mass spectrometry (UPLC-ESI-MS/ MS).