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