Poly(lactic-co-glycolic) acid nanoparticles improve oral bioavailability of hypocrellin A in rat

Hypocrellin A (HA), a perihydroxylated polycyclic quinone isolated from the fungus of Shiraia bambusicola, exhibits a wide spectrum of biological activities in pre-clinical studies. However, poor water solubility is a major clinical constraint factor of HA, leading to unpredictable bioavailability. In this study, HA-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA/HA NPs) were prepared by the single-emulsion solvent-evaporation technique. Characterization of PLGA/HA NPs showed that HA was successfully encapsulated on the PLGA. The drug-loading content and encapsulation efficiency (EE) were 7.0% and 57.5%, respectively. The in vitro release profile demonstrated that HA was released more slowly from nanoparticles in pH 1.5 and pH 6.8 than in pH 7.4. Furthermore, the highest solubility of PLGA/HA NPs in aqueous solution was approximately 35.67-fold that of native HA (n-HA). PLGA/HA NPs had more superior stability compared with n-HA in physiological conditions. In this paper, a sample and sensitive LC-MS/MS method was validated for the first time to quantify HA in rat plasma. The pharmacokinetic parameters and bioavailability of HA between PLGA/HA NPs and n-HA were compared after oral administration in rat. The results implied that the relative bioavailability of PLGA/HA NPs was 2.67-fold that of n-HA, and PLGA/HA NPs had a longer half-life. Therefore, these results suggested that PLGA-blend nanoparticles improved the solubility, stability and bioavailability of HA, and could become a potential and promising carrier for the oral delivery of HA.