Purpose: Madecassic acid (MCA) is a natural triterpenoid isolated from centellae herba that has diverse biological effects, such as anti-inflammatory, antioxidant, and anticancer activities. However, the efficacy of MCA is limited by low oral bioavailability caused by its extremely poor aqueous solubility. This study aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) for MCA to improve its oral absorption.
Methods: The utilized oil phases, surfactants, and co-surfactants for SNEDDS were selected based on the solubility of MCA and emulsification efficiency. The optimized formulation was characterized for pharmaceutical properties and its pharmacokinetic behavior was examined in rats. Besides, the intestinal absorption property of MCA was investigated using in situ single-pass intestinal perfusion and intestinal lymphatic transport.
Results: The optimized nanoemulsion formula consists of Capryol 90:Labrasol:Kolliphor ELP:Transcutol HP in a weight ratio of 1:2.7:2.7:3.6 (w/w/w/w). MCA-loaded SNEDDS presented a small droplet size (21.52 ± 0.23 nm), with a zeta potential value of − 3.05 ± 0.3 mV. Compared with pure MCA, SNEDDS had a higher effective permeability coefficient and showed 8.47-fold and 4.01-fold of maximum plasma concentration (C_max) and area under the plasma concentration-time curve (AUC), respectively. Cycloheximide was pretreated before the experiment to evaluate the degree of lymphatic uptake. The results showed that cycloheximide greatly influenced the absorption of SNEDDS, resulting in 82.26% and 76.98% reduction in C_max and AUC, respectively.
Conclusion: This study reports the MCA-loaded SNEDDS with distinctly enhanced in vitro and in vivo performance compared with pure MCA and concludes that the SNEDDS formulation could be a viable and effective strategy for improving the dissolution rate and bioavailability of poor aqueous-soluble ingredients.
Keywords: madecassic acid, self-nanoemulsifying drug delivery system, pharmacokinetics, intestinal lymphatic transport