In vitro and in vivo implications of rationally designed bromelain laden core-shell hybrid solid lipid nanoparticles for oral administration in thrombosis management

Abstract

Bromelain, a dietary supplement of cysteine protease family having promising results against thrombosis, is gaining attention. Yet poor mechanical stability, gastric instability, high oral dose and poor patient compliance restricted its clinical application. Therefore, acid stable bromelain loaded hybrid solid lipid nanoparticles (Br-HNPs) were fabricated and characterized for their contribution to in-vivo stability and therapeutic efficacy in thrombosis management. Comprehensive optimization of various process and formulation variables ensued the formation of nano-sized (120.56 ± 40.12 nm) Br-HNPs with entrapment efficiency of 86.32 ± 5.56%. Spherical core shell framework of Br-HNPs prolonged drug release and provided in-vivo and storage stability at room temperature. Br-HNPs significantly inhibited platelet aggregation without affecting bleeding time and dissolved thrombus at 1.91-fold higher efficacy compared to bromelain. Furthermore, Br-HNPs prevented hypercoagulation states and suppressed cytokines production significantly (P < .05) contributing to its antiplatelet activity. These findings indicated that Br-HNPs could serve as a promising alternative to commercial therapies for management of thrombotic disorders.