Eudragit S100-coated liposomes: a pH-responsive strategy to overcome dabigatran etexilate's oral bioavailability challenge.

OBJECTIVES

Dabigatran etexilate (DAB), a direct thrombin inhibitor, exhibits limited oral bioavailability (6%-7%), mostly attributable to pH-dependent solubility. To address this issue, Eudragit S100 (EU)-coated liposomes were engineered to safeguard DAB-loaded nanocarriers in the stomach and provide targeted release in the intestine, where absorption occurs through several mechanisms.

METHODS

Liposomal vesicles were prepared using the conventional thin film hydration method. The developed formulations were subjected to physicochemical characterization, which included Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), zeta potential analysis, particle size measurement, polydispersity index (PDI) assessment, entrapment efficiency (EE%), and transmission electron microscopy (TEM).

KEY FINDINGS: The selected formulation, EU@DAB-Lip4, exhibited advantageous properties: minimal particle size (136.9 nm), high EE (92.67%), and colloidal stability (zeta potential -17.3 mV). In vitro release demonstrated pH-responsive behaviour, with low gastric release (12.8% at 2 hr) and enhanced intestinal release (75.5% at pH 7.4). Pharmacokinetic studies in rats demonstrated a 5.6-fold and 2.7-fold enhancement in bioavailability for EU@DAB-Lip4 relative to DAB-Lip and DAB suspension, respectively, as indicated by elevated Cmax (2664 vs. 891 and 554 ng/ml) and AUC₀-∞ (21 020 vs. 7236 and 3749 ng.hr/ml).

CONCLUSIONS

EU-coated liposomes constitute a viable platform for enhancing DAB bioavailability and therapeutic efficacy.