Design of enzyme decorated mucopermeating nanocarriers for eradication of H. pylori infection.

The study was aimed to develop amoxicillin (AM) loaded thiomer based mucopermeating and mucoadhesive nanocarrier system that allows it to reach the bacterium, hiding in deeper mucus layers and extends its availability at infection site. Amoxicillin loaded nanocargoes were prepared using unmodified polycarbophil (PCP), thiolated polycarbophil (PCP-Cys), and papain modified thiolated polycarbophil (PCP-Cys-PAP) by ionic gelation method and processed for in vitro and ex vivo and in vivo characterization. All the nanocargoes were in size range of 111–288 nm. Drug loaded papain modified thiolated polycarbophil (AM-PCP-Cys-PAP) based nanocargoes showed an entrapment efficiency of 78 ± 7.2%, a zeta potential of − 13.4 mV and spherical shape. Both AM-PCP-Cys and AM-PCP-Cys-PAP exhibited a sustained release of drug up to 48 h and AM-PCP-Cys-PAP nanocargoes showed significant stability in acidic pH as compared to pure drug. Rheological investigation demonstrated a twofold higher mucoadhesion for thiolated polycarbophil nanocargoes. Ex vivo muco-penetration studies demonstrated deepest permeation of papain modified nanocargoes into the mucus. Cytotoxicity analysis showed that nanocarrier formulations were non-toxic to Caco-2 cells and maintained cell viability after 48 h. In vitro growth inhibition assay for H. pylori exhibited better efficacy for AM-PCP-Cys-PAP nanocargoes in terms of improved stability along with complete eradication of bacteria over prolonged period of time. In vivo acute toxicity studies on vital organs of mice exhibited no significant change in cell morphology. In vivo clearance study showed that AM-PCP-Cys-PAP nanoformulation was successful in complete eradication of bacteria. Based on above findings, amoxicillin loaded papain modified thiolated polycarbophil nanocarrier system was able to completely eradicate H. pylori infection that was attributed to its enhanced mucopermeating and mucoadhesive nature. The functionalized nanocarriers showed an interesting future potential for infectious therapy. [ABSTRACT FROM AUTHOR]