Development of phospholipon®90H complex nanocarrier with enhanced oral bioavailability and anti-inflammatory potential of genistein

Abstract

Genistein (GEN), an isoflavonoid, offers multifunctional biological activities. However, its poor oral bioavailability, aqueous solubility, extensive metabolism, and short half-life restricted its clinical use. Therefore, the Phospholipon ® 90H complex of genistein (GPLC) was prepared to enhance its biopharmaceutical properties and anti-inflammatory activity. GPLC was characterized by employing particle size and zeta potential, Fourier transforms infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry, proton nuclear magnetic resonance, aqueous solubility, in vitro dissolution, ex vivo permeation, oral bioavailability and in vivo anti-inflammatory activity. The complex showed high entrapment of GEN (∼97.88% w/w) within the Phospholipon ® 90H matrix. Particle size and zeta potential studies confirmed the small particle size with the modest stability of GPLC. The characterization analysis supported the formation of GPLC through the participation of hydrogen bonding between GEN and Phospholipon ® 90H. GPLC significantly enhanced the aqueous solubility (∼2-fold) compared to GEN. Dissolution studies revealed that GPLC drastically improved the GEN dissolution rate compared to GEN. Likewise, the complex improved the permeation rate across the membrane compared to GEN. GPLC formulation significantly enhanced the oral bioavailability of GEN via improving its Cmax, tmax, AUC, half-life and mean residence time within the blood circulation compared to GEN. The GPLC (∼20 mg/kg, p.o.) remarkably inhibited the increase in paw edema up to 5 h, compared to GEN and diclofenac. Results suggest that the Phospholipon ® 90 complex is a superior and promising carrier for enhancing the biopharmaceutical parameters of GEN and other bioactive with similar properties.

A comparative study on the preparation and evaluation of solubilizing systems for silymarin

“…[18]. This interaction promotes the integration of the SM molecule into the polar head of the phospholipid, while the hydrophobic tail portion of the phospholipid ensures the proper orientation of this complex, leading to the formation of an amphiphilic complex that enhances transportation from an aqueous environment to a lipid-soluble environment [45]. Following the formation of the PC, the constituents' membrane permeability and oil-water partition coe cient would experience a substantial increase.…”

An assessment of the factors contributing to the unavailability of drugs at outpatient pharmacy of tertiary care hospital: an observational study

“…A number of studies related to shortages in outpatient pharmacy were reported. [7][8][9][10][11] This essay can be used as a reference to highlight all the various factors that should be considered while formulating a definition that will be used throughout the EU. 3…”

Natural Flavonoids and Ferroptosis: Potential Therapeutic Opportunities for Human Diseases

“…142−145 For example, phospholipon 90H complex of genistein not only improved the water solubility, dissolution rate, membrane permeation rate, and oral bioavailability of genistein but also significantly enhanced its anti-inflammatory activity. 146 Notably, Fe 2 O 3 /Fe 3 O 4 @mSiO 2 nanoparticles of apigenin had good magnetic targeting and showed stronger antitumor activity by promoting ferroptosis in A549 cells. 147 In addition, the existing research on flavonoids targeting ferroptosis mainly focuses on animal experiments and in vitro cell experiments, so there is still a lack of scientific evidence to support their clinical application.…”

“…As an excellent natural product, flavonoids are beneficial to human health and have few adverse side effects. , It is important to recognize that the bioavailability of most dietary flavonoids is low, which is related to factors such as structure, glycosylation, and colonic microbial metabolism . Structural modification and novel delivery systems are common methods to improve the bioavailability and efficacy of flavonoids. − For example, phospholipon 90H complex of genistein not only improved the water solubility, dissolution rate, membrane permeation rate, and oral bioavailability of genistein but also significantly enhanced its anti-inflammatory activity . Notably, Fe 2 O 3 /Fe 3 O 4 @mSiO 2 nanoparticles of apigenin had good magnetic targeting and showed stronger antitumor activity by promoting ferroptosis in A549 cells .…”