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Pharmaceutics
Volume 11
Issue 1
10.3390/pharmaceutics11010015
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Open AccessArticle

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

by
Li-qian Ci
1,2,†,
Zhi-gang Huang
1,†,
Feng-mei Lv
2,
Jun Wang
2,
Ling-lin Feng
3,
Feng Sun
4,
Shui-juan Cao
5,
Zhe-peng Liu
2,
Yu Liu
1,*,
Gang Wei
1 and
Wei-yue Lu
1
1
Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China
2
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
3
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
4
Chinese Academy of Sciences Shanghai Institute of Materia Medica, Shanghai 201203, China
5
Experimental Teaching Center, School of Pharmacy, Fudan University, Shanghai 201203, China
*
Author to whom correspondence should be addressed.
†
Equally contributing authors.
Pharmaceutics 2019, 11(1), 15; https://doi.org/10.3390/pharmaceutics11010015
Received: 14 November 2018 / Revised: 7 December 2018 / Accepted: 9 December 2018 / Published: 4 January 2019
(This article belongs to the Special Issue Transmucosal Absorption Enhancers in the Drug Delivery Field)
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Abstract

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 ([email protected]2) 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 [email protected]2 and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of [email protected]2 and the change in the size distribution on mixing of [email protected]2 and mucin. Cellular uptake, growth inhibition, and apoptosis induction in cervicovaginal cancer-related cells demonstrated the superiority of [email protected]2 over unmodified nanocrystals. For practical intravaginal administration, [email protected]2 was dispersed in Pluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature and sustained-release profiles. In comparison with unmodified nanocrystals, [email protected]2 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 [email protected]2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer via intravaginal administration. View Full-Text
Keywords: mucoadhesiveness; cervicovaginal tumors; cationic functionalization; imatinib; nanocrystals; in situ hydrogel mucoadhesiveness; cervicovaginal tumors; cationic functionalization; imatinib; nanocrystals; in situ hydrogel
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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MDPI and ACS Style

Ci, L.-q.; Huang, Z.-g.; Lv, F.-m.; Wang, J.; Feng, L.-l.; Sun, F.; Cao, S.-j.; Liu, Z.-p.; Liu, Y.; Wei, G.; Lu, W.-y. Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer. Pharmaceutics 2019, 11, 15. https://doi.org/10.3390/pharmaceutics11010015

AMA Style

Ci L-q, Huang Z-g, Lv F-m, Wang J, Feng L-l, Sun F, Cao S-j, Liu Z-p, Liu Y, Wei G, Lu W-y. Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer. Pharmaceutics. 2019; 11(1):15. https://doi.org/10.3390/pharmaceutics11010015

Chicago/Turabian Style

Ci, Li-qian; Huang, Zhi-gang; Lv, Feng-mei; Wang, Jun; Feng, Ling-lin; Sun, Feng; Cao, Shui-juan; Liu, Zhe-peng; Liu, Yu; Wei, Gang; Lu, Wei-yue. 2019. "Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer" Pharmaceutics 11, no. 1: 15. https://doi.org/10.3390/pharmaceutics11010015

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