International Journal of Nanomedicine (May 2023)
Self-Nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Madecassic Acid: In vitro and in vivo Evaluation
Abstract
Li Lin,1,* Qingyong Chen,1,* Yue Dai,2 Yufeng Xia1 1Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China; 2Department of Traditional Chinese Medicine and Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yufeng Xia, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China, Tel +862583271400, Fax +862585301528, Email [email protected]: 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 (Cmax) 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 Cmax 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
