Preparation, Characterization, and In Vivo Evaluation of an Oral Triptolide Nanomatrix System for Rheumatoid...

Background: Triptolide (TP), a principal bioactive component of Tripterygium wilfordii, exhibits potent anti-inflammatory activity. However, its application is still limited due to its poor solubility and systemic toxicity, primarily caused by uncontrolled absorption after oral administration. Our previously established oral nanomatrix system, composed mainly of commercially available nanoporous Sylysia and Eudragit^®, can not only enhance the in vitro dissolution of poorly water-soluble drugs, but also modulate their absorption sites in gastrointestinal tract. Methods: We prepared a TP nanomatrix system using Sylysia 350 and Eudragit^® L100 to modulate TP's dissolution in order to overcome TP's limitation. Then, the nanomatrix was evaluated through in vitro dissolution, physicochemical characterization, and in vivo pharmacokinetic study, and then was comprehensively assessed for efficacy and safety in a rat model of rheumatoid arthritis. Results: TP nanomatrix system exhibited a marked increase in drug dissolution in various media, especially in pH 6.8 medium. The nanomatrix system showed better oral bioavailability than free TP, yet with no toxicity observed. Conclusions: This study developed a simple oral nanomatrix system of TP with enhanced anti-inflammatory efficacy without observed toxicity, and provided a potential strategy to progress the clinical translation of TP products.