Dual mechanistic approach utilizing pH- and time- responsive bromelain laden polymeric nanoparticles for colon cancer management

• pH-time responsive bromelain loaded polymeric nanocarriers (Br-PNPs) were fabricated to enable site-specific colon delivery. • Br-PNPs sustained release behavior and mucoadhesivity enhanced cytotoxic potential of bromelain on HCT-116 cell lines. • In vivo studies demonstrated significant reduction of tumor burden, aberrant crypt foci and oxidative stress in DMH+DSS rat model. • Lyophilized Br-PNPs present a promising colon specific oral delivery system for effective management of colon cancer. Emerging evidences confirming bromelain’s potential to induce apoptosis and inhibit tumor progression highlights its prospective as adjunctive therapeutic in colorectal cancer malignancies. Despite, high oral doses coupled with poor bioavailability remarkably limits bromelain’s clinical utility, underscoring the necessity of use of innovative delivery strategies. Therefore, the current invention was designed to develop dual pH- and time-responsive bromelain-loaded nanoformulation (Br-PNPs) for controlled and precise delivery to colon with high drug loading capacity and enhanced therapeutic efficacy. pH responsive spherical shaped mucoadhesive nanosized (89.02±6.23 nm) Br-PNPs underscores their potential of minimizing gastric exposure while swelling and mucoadhesivity assured sustained release in colon. Lower IC 50 (16.25µg/ml) along with enhanced colon drug concentration attained by Br-PNPs assured their effective colon targeting potential. Br-PNPs significantly reduced disease activity index, tumor burden, aberrant crypt foci and hyperplastic lesions in colon alongside oxidative stress and immunological biomarkers in chemically induced colon cancer model (DMH+DSS) in Wistar rat. The preclinical findings suggested that Br-PNPs have opened up new horizons for establishment of promising contender for colon cancer management in near future.