Vaginal delivery of paclitaxel via nanoparticles with non-mucoadhesive surfaces suppresses cervical tumor growth.

Mark McIntosh,'s picture
PubMed URL: 
http://www.ncbi.nlm.nih.gov/pubmed/24339398
Author: 
Hanes J
Author List: 
Yang M
Yu T
Wang YY
Lai SK
Zeng Q
Miao B
Tang BC
Simons BW
Ensign LM
Liu G
Chan KW
Juang CY
Mert O
Wood J
Fu J
McMahon MT
Wu TC
Hung CF
Hanes J
Journal: 
Adv Healthc Mater
PubMed ID: 
24339398
Pagination: 
1044-52
Volume: 
3
Issue: 
7
Abstract: 
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.
Published Date: 
July, 2014

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