Phytophospholipid Complex of Caffeic Acid: Development, In vitro Characterization, and In Vivo Investigation of Antihyperlipidemic and Hepatoprotective Action in Rats

Caffeic acid (CA), a hydroxycinnamic acid possessing a variety of pharmacological activities, has caused a growing interest for the treatment of hyperlipidemia and associated conditions. This work endeavored to develop a novel formulation of CA-Phospholipon® 90H complex (CA-PC) using a solvent evaporation method. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectrophotometry (FTIR), and powder X-ray powder diffraction (PXRD) was carried to confirm the formation of CA-PC.

The CA-PC was functionally evaluated in terms of solubility, in vitro and ex vivo drug release, and in vivo bioavailability and efficacy studies. SEM, DSC, FTIR, and XRD studies indicated the physical interaction of CA with Phospholipon® 90H to form a complex. Dynamic light scattering (DLS) studies described particle size of 168 ± 3.9 nm with a monodisperse distribution (PDI 0.17) and a negative zeta-potential of − 16.6 ± 2.1 mV. The phospholipid complex significantly improved (4.2-fold) the solubility of CA. In vitro and ex vivo dissolution studies of the formulated CA-PC revealed a significantly higher release compared with the pure CA. The pharmacokinetic study of CA-PC in rats demonstrated a significant increase (4.79-fold) in oral bioavailability when compared with pure CA as well.

Additionally, a significant improvement in serum lipid profile, serum liver biomarker enzyme levels and, restoration of hepatic tissue architecture to normal, in high-fat diet (HFD) induced hyperlipidemic model was obtained upon CA-PC administration when compared with pure CA. These findings indicated that CA-PC would serve as an effective and promising formulation for CA delivery with improved antihyperlipidemic and hepatoprotective activity.

This interesting example on the exploration of phospholipids to make high drug load complexes with increased oral bioavailability was provided by Lipoid.

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Article information: Mangrulkar, S., Shah, P., Navnage, S. et al. Phytophospholipid Complex of Caffeic Acid: Development, In vitro Characterization, and In Vivo Investigation of Antihyperlipidemic and Hepatoprotective Action in Rats. AAPS PharmSciTech 22, 28 (2021). https://doi.org/10.1208/s12249-020-01887-7