The present study was carried out to investigate the potential of cationic functionalization\non imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion\nof cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2)\nwere prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential,\nand relatively high drug content with the aid of the polydopamine-coating technique. Efficient\ninteraction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related\nto the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution\non mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis\ninduction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over\nunmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in\nPluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature\nand sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2\nexhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal\nresidence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model\ntumors indicated by smaller tumor size, longer median survival time, and more intratumor\napoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed\nNC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer\nvia intravaginal administration.
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