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Vaginal Delivery of Paclitaxel via Nanoparticles with Non‐Mucoadhesive Surfaces Suppresses Cervical Tumor Growth
Author(s) -
Yang Ming,
Yu Tao,
Wang YingYing,
Lai Samuel K.,
Zeng Qi,
Miao Bolong,
Tang Benjamin C.,
Simons Brian W.,
Ensign Laura M.,
Liu Guanshu,
Chan Kannie W.Y.,
Juang ChihYin,
Mert Olcay,
Wood Joseph,
Fu Jie,
McMahon Michael T.,
Wu T.C.,
Hung ChienFu,
Hanes Justin
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201300519
Subject(s) - paclitaxel , plga , in vivo , drug delivery , mucoadhesion , mucus , pharmacology , cervical cancer , poloxamer , medicine , nanoparticle , chemotherapy , drug carrier , drug , chemistry , cancer , materials science , biology , nanotechnology , polymer , ecology , microbiology and biotechnology , organic chemistry , copolymer
Local delivery of chemotherapeutics in the cervicovaginal tract using nanoparticles may reduce adverse side effects associated with systemic chemotherapy, while improving outcomes for early‐stage cervical cancer. It is hypothesized here that drug‐loaded nanoparticles that rapidly penetrate cervicovaginal mucus (CVM) lining the female reproductive tract will more effectively deliver their payload to underlying diseased tissues in a uniform and sustained manner compared with nanoparticles that do not efficiently penetrate CVM. Paclitaxel‐loaded nanoparticles are developed, composed entirely of polymers used in FDA‐approved products, which rapidly penetrate human CVM and provide sustained drug release with minimal burst effect. A mouse model is further employed with aggressive cervical tumors established in the cervicovaginal tract to compare paclitaxel‐loaded poly(lactic‐ co ‐glycolic acid) (PLGA) nanoparticles (conventional particles, or CP) and similar particles coated with Pluronic F127 (mucus‐penetrating particles, or MPP). CP are mucoadhesive and, thus, aggregated in mucus, while MPP achieve more uniform distribution and close proximity to cervical tumors. Paclitaxel‐MPP suppress tumor growth more effectively and prolong median survival of mice compared with unencapsulated paclitaxel or paclitaxel‐CP. Histopathological studies demonstrate minimal toxicity to the cervicovaginal epithelia, suggesting paclitaxel‐MPP may be safe for intravaginal use. These results demonstrate the in vivo advantages of polymer‐based MPP for treatment of tumors localized to a mucosal surface.