Harnessing Hybrid Niosomes for Improved Oral Bioavailability of an Anticoagulant: Design, Optimization and In-Vivo Pharmacokinetics and Pharmacodynamics Evaluations

Abstract Venous thromboembolism (VTE) and pulmonary embolism (PE), remains a major global health burden, necessitating prolonged and reliable anticoagulant therapy. Although Apixaban (APX) is a cornerstone oral anticoagulant for VTE management, its therapeutic performance is limited by poor aqueous solubility and low oral bioavailability. To overcome these challenges, this study introduces a hybrid niosomal delivery system designed to enhance the absorption and systemic persistence of APX. The system was engineered by integrating hybrid of surfactants together with cholesterol to form a stable, vesicular matrix. Formulations were prepared via the ethanol injection method and systematically optimized using a 2 3 factorial design, assessing the influence of Span 60 concentration (Factor-A), cholesterol: drug ratio (Factor-B), and Tween 80 amount (Factor-C). The optimized formulation achieved a desirability score of 0.738, demonstrating high entrapment efficiency (72.82%), nanoscale particle size (160.05 nm) and a distinctly stable potential (–47.15 mV). TEM imaging confirmed spherical vesicles, and in-vitro release studies revealed a biphasic pattern characterized by an initial burst followed by sustained diffusion. Pharmacodynamics evaluations showed that the optimized formula produced a 1.55-fold increase in cuticle bleeding time (CBT) and a 1.65-fold prolongation in prothrombin time (PT) relative to the APX suspension. Pharmacokinetics assessments further demonstrated enhanced oral bioavailability, evidenced by increased AUC and C max , along with reduced terminal elimination rate constant (λz) and extended systemic retention. Overall, the developed hybrid niosomes present a promising oral platform for APX delivery, offering improved absorption, and sustained therapeutic action. Graphical Abstract