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


Chlorogenic 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.


Higher 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.


The 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.


CGA was obtained from Chemsworth, India. Soyabean phospholipid LIPOID® S100 and hydrogenated phospholipid Phospholipon® 90H were obtained as gratis samples from Lipoid, Germany. DPPH (2-diphenyl-1-picrylhydrazyl), ferrozine and ferric chloride were obtained from SD fine chemicals, India. Dichloromethane and N-hexane were purchased from Merck, India. Rhodamine 6G and sinapic acid (Internal standard) D7927 were procured from Sigma-Aldrich, USA. Silverex® heal hydrogel (1% colloid silver) (Sun pharmaceuticals In. Ltd.) was purchased from local pharmacy shop. MTT(3-(4,5-dimethylthiazol-2-yl)- 2,5- diphenyltetrazolium bromide) was purchased from Thermo Fisher scientific, India. MEM (Minimum Essential Medium Eagle) and RPMI-1640 (Roswell Park Memorial Institute) medium, foetal bovine serum (FBS) were obtained from HiMedia Lab, India. While all other reagents used in the study were of analytical grade. HL-60 (human leukaemia cell line) and HeLa (Henrietta Lacks cervical cancer cell line) were obtained from National Centre for cell lines, India.

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Trivedi, H.R., Puranik, P.K. Chlorogenic acid-optimized nanophytovesicles: a novel approach for enhanced permeability and oral bioavailability. Futur J Pharm Sci 9, 116 (2023).

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