A Bubble-Driven Drug Delivery System Enhances Oral Absorption and Antipyretic Efficacy of Poorly Water-Soluble Andrographolide

Purpose: While bubble-carrier systems hold great promise for enhancing the oral bioavailability of poorly water-soluble drugs, a deeper understanding of their underlying absorption mechanisms is still required. This study aimed to address this gap by developing a bubble-driven delivery system (BDDS) using the poorly water-soluble andrographolide (AG) as a model drug, and systematically evaluating its solubilization capacity and intestinal permeability. Methods: = 6:5) and bile salts (sodium deoxycholate, SDC). Its performance was comprehensively assessed via in vitro dissolution tests, an everted intestinal sac assay, Caco-2 cell monolayer experiments, pharmacokinetic studies, and yeast-induced fever rat models. Results: The BDDS achieved 75.0%-88.7% dissolution in gastrointestinal pH media, which was markedly superior to that of commercial dripping pills (DP; 30.5-50.2%). Its apparent permeability coefficient was 7.7-fold and 3.6-fold higher than that of free AG and DP, respectively. Transport studies indicated that SDC enhanced AG permeability primarily via the apical sodium-dependent bile acid transporter (ASBT)-mediated pathway, a mechanism further confirmed by inhibition with linerixibat. The relative oral bioavailability of BDDS versus DP reached 257.1%. BDDS demonstrated enhanced efficacy by significantly inhibiting key pro-inflammatory cytokines and thermoregulatory mediators in yeast-induced fever rats. Discussion: bubbles) and permeability (via ASBT transport), outperforming conventional formulations in terms of preparation simplicity and storage stability. Conclusion: BDDS is a promising strategy to improve oral absorption and therapeutic efficacy of BCS Class IV drugs like AG, with ASBT-mediated transport as a key mechanism.