[P001] Poster

12:10 PM - 1:00 PM JST(3:10 AM - 4:00 AM UTC)

[P01-119] A Water-Insoluble Bentonite–Liposome Composite Enables Intestine-Selective Liposome Release and Enhances Oral Bioavailability of Apatinib

○Pil-Jae Song¹, Ho-Sup Jung¹, Dae-Duk Kim¹ (1. College of Pharmacy, Natural Products Research Institute, Seoul National University (Korea))

Keywords:

Bentonite,Liposome,Water-insoluble matrix,Intestine-selective release,Oral bioavailability,Apatinib

Oral liposomal drug delivery systems hold considerable promise for improving the bioavailability of poorly water-soluble drugs; however, their clinical translation remains limited by instability during storage and premature degradation in the gastric environment. Conventional proliposome formulations rapidly and uncontrollably generate liposomes upon contact with gastric fluid, increasing the risk of drug precipitation prior to intestinal absorption. To address these limitations, we developed a novel apatinib-loaded liposome–bentonite composite (ALBC) that exploits the pH-responsive surface charge behavior of phosphatidylcholine to achieve intestine-selective liposome release. Apatinib (APT), a BCS Class II anticancer agent, was encapsulated in soy phosphatidylcholine/cholesterol-based liposomes (A-lipo) using thin-film hydration followed by probe sonication and membrane extrusion, achieving an entrapment efficiency of 86.5 ± 0.1%. A-lipo was subsequently adsorbed onto calcium-type bentonite (BT) under acidic conditions via electrostatic interactions, utilizing the protonation-induced cationic surface charge of phosphatidylcholine at gastric pH. The resulting ALBC was obtained as a free-flowing lyophilized powder compatible with conventional solid oral dosage forms. Transmission electron microscopy (TEM) revealed negligible liposome release at pH 1.2, whereas pronounced liposome regeneration was observed at intestinal pH 6.8. In vitro release studies confirmed that APT released under intestinal conditions remained predominantly encapsulated within intact liposomes. In addition, ALBC maintained physicochemical stability, with no significant changes in crystallinity or drug content over 21 days. In vivo pharmacokinetic evaluation in Sprague–Dawley rats after oral administration at 10 mg/kg dose demonstrated that ALBC significantly enhanced systemic APT exposure compared with a plain drug suspension (AUC_inf: 1703 ± 917 vs. 549 ± 122 ng·h/mL; 3.1-fold increase, p < 0.05), with a delayed T_max consistent with intestinally triggered release. A control formulation without prior liposome formation did not improve oral bioavailability, highlighting the importance of maintaining the intact liposomal structure for enhanced absorption. Collectively, these findings establish BT as a water-insoluble matrix capable of stabilizing oral liposomes and enabling site-specific intestinal delivery, offering a broadly applicable platform for poorly water-soluble therapeutics.