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

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 23 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 Cmax, 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. • Hybrid niosomes were successfully engineered to enhance the oral delivery and therapeutic persistence of Apixaban. • A 23 factorial design enabled precise optimization of Span 60 concentration, cholesterol: drug ratio, and Tween 80 levels, yielding a formulation with high entrapment efficiency (72.82%), nanoscale size (160.05 nm), and robust stability (−47.15 mV). • The optimized niosomal system exhibited spherical morphology and a biphasic release pattern, combining rapid initial diffusion with sustained long-term release. • Pharmacodynamics studies demonstrated pronounced anticoagulant enhancement, achieving 1.55-fold longer cuticle bleeding time and 1.65-fold prolonged prothrombin time compared with Apixaban suspension. • Pharmacokinetic evaluation revealed markedly improved oral bioavailability, increased Cmax and AUC and reduced elimination rate, confirming enhanced systemic retention of Apixaban.