Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer

Pharmaceutics

Zhi-gang Huang¹  Jun Wang¹  Zhe-peng Liu²  Wei-yue Lu³  Feng-mei Lv³  Li-qian Ci³  Yu Liu⁴  Shui-juan Cao⁵  Feng Sun⁶  Gang Wei⁶  Ling-lin Feng⁶ 

[1] Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China;Chinese Academy of Sciences Shanghai Institute of Materia Medica, Shanghai 201203, China;;Department of Pharmaceutics, School of Pharmacy, Fudan University &Experimental Teaching Center, School of Pharmacy, Fudan University, Shanghai 201203, China;NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Room 904, No 1 Research Building, 2140 Xietu Road, Shanghai 200032, China;School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China;

关键词: mucoadhesiveness;    cervicovaginal tumors;    cationic functionalization;    imatinib;    nanocrystals;    in situ hydrogel;   

DOI  :  10.3390/pharmaceutics11010015

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown