Chlorogenic acid-optimized nanophytovesicles: a novel approach for enhanced permeability and oral bioavailability

Abstract

BackgroundChlorogenic acid, a phenolic derivative, shows excellent pharmacological properties. However, poor lipidic solubility, permeability, and oral bioavailability restrict its clinical use. Therefore, two different phospholipids—Phospholipon® 90H and LIPOID® S100 nanophytovesicles (NPVs)—were optimized, formulated and compared with central composite design for improved biopharmaceutical properties, antioxidant, anticancer and wound-healing activities.ResultsHigher entrapment (> 95%) and partition coefficient values were obtained with optimized CGA 90H NPVs and S100 NPVs. Particle size and zeta potential values confirmed small particle size(≅ 450 nm) with optimum stability. Non-covalent interactions between CGA and both phospholipids were confirmed with Fourier transform infrared spectrophotometry, differential scanning calorimetry and proton nuclear magnetic resonance. NPVs significantly enhanced the lipidic solubility (> 25 times) supported by high-performance thin-layer chromatography. A sustained dissolution and diffusion release were obtained with NPVs as compared to pure CGA. Likewise, ≅ twofold increase in permeability was obtained, supported by confocal microscopy. Enhanced oral bioavailability of CGA with improved Cmax, Tmax, AUC, half-life values was obtained with NPVs along with IVIV correlation. Enhanced DPPH radical scavenging and Fe2+ chelation ability were obtained with CGA 90H NPVs > CGA S100 NPVs, with lower IC50 values in HeLa and HL-60 cell lines (< 0.75 times) as compared to CGA in MTT(3-(4,5-dimethylthiazol-2-yl)- 2,5- diphenyltetrazolium bromide) assay. Higher wound contraction percentages were observed at day 3 with CGA S100 NPVs (71.56%) > CGA 90H NPVs (34.0%) in wound-healing studies.ConclusionsThe formulated NPVs exhibited efficiency of Phospholipon®90 H in enhancing oral bioavailability and LIPOID® S100 in increasing transdermal permeability, thus proving as promising carriers for enhancing biopharmaceutical and pharmacological properties of chlorogenic acid.