Biopharmaceutical Profiling of Herpetrione: A BCS II Properties and P-gp Substrate Guiding Nanoparticle Design.

Objectives

Herpetrione (HPE) is a bioactive lignan recognized for its hepatoprotective properties; however, it exhibits limited oral bioavailability. This study aimed to classify HPE within the framework of the biopharmaceutics classification system (BCS) and to develop a nanoparticle formulation.

Methods

To this end, a comprehensive investigation was conducted, encompassing computer prediction analysis, equilibrium solubility measurements across the gastrointestinal pH range, Caco-2 bidirectional transportation, in situ single-pass intestinal perfusion (SPIP), and molecular docking with P-glycoprotein (P-gp).

Results

In silico analyses suggested that HPE possesses low solubility and low permeability characteristics. Experimental assays revealed pH-dependent solubility and inherently low aqueous dissolution. Unlike the computer prediction results, Caco-2 studies revealed moderate permeability but a high efflux ratio, suggestive of possible P-gp substrate activity for HPE, a finding further supported by molecular docking simulations. Conversely, SPIP studies demonstrated that the effective permeability (Peff) of jejunal intestinal segments exceeded the high-permeability threshold, thereby classifying HPE as a high-permeability drug. Based on these findings, HPE was classified as a BCS class II compound. To overcome its solubility-limited absorption, a nanoparticle was developed, resulting in a marked enhancement of both solubility and dissolution rates.

Conclusions

These findings underscore the importance of integrating experimental biopharmaceutical evaluations with computational tools when designing delivery systems for natural products.