Vaginal Delivery of Paclitaxel via Nanoparticles with Non-Mucoadhesive Surfaces Suppresses Cervical Tumor Growth

Ming Yang, Tao Yu, Ying Ying Wang, Samuel K. Lai, Qi Zeng, Bolong Miao, Benjamin C. Tang, Brian W. Simons, Laura Ensign-Hodges, Guanshu Liu, Kannie W Y Chan, Chih Yin Juang, Olcay Mert, Joseph Wood, Jie Fu, Michael T Mcmahon, Tzyy Choou Wu, Chien-Fu Hung, Justin S Hanes

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1044-1052
Number of pages9
JournalAdvanced healthcare materials
Volume3
Issue number7
DOIs
StatePublished - 2014

Fingerprint

Paclitaxel
Nanoparticles
Mucus
Tumors
Growth
Neoplasms
UCON 50-HB-5100
Polymers
Chemotherapy
Poloxamer
Linings
Toxicity
Uterine Cervical Neoplasms
Pharmaceutical Preparations
Tissue
Epithelium
Acids
Drug Therapy

Keywords

  • Biodegradable polymers
  • Cancer
  • Chemotherapy
  • Controlled release
  • Drug delivery

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Pharmaceutical Science

Cite this

Vaginal Delivery of Paclitaxel via Nanoparticles with Non-Mucoadhesive Surfaces Suppresses Cervical Tumor Growth. / Yang, Ming; Yu, Tao; Wang, Ying Ying; Lai, Samuel K.; Zeng, Qi; Miao, Bolong; Tang, Benjamin C.; Simons, Brian W.; Ensign-Hodges, Laura; Liu, Guanshu; Chan, Kannie W Y; Juang, Chih Yin; Mert, Olcay; Wood, Joseph; Fu, Jie; Mcmahon, Michael T; Wu, Tzyy Choou; Hung, Chien-Fu; Hanes, Justin S.

In: Advanced healthcare materials, Vol. 3, No. 7, 2014, p. 1044-1052.

Research output: Contribution to journalArticle

Yang, Ming ; Yu, Tao ; Wang, Ying Ying ; Lai, Samuel K. ; Zeng, Qi ; Miao, Bolong ; Tang, Benjamin C. ; Simons, Brian W. ; Ensign-Hodges, Laura ; Liu, Guanshu ; Chan, Kannie W Y ; Juang, Chih Yin ; Mert, Olcay ; Wood, Joseph ; Fu, Jie ; Mcmahon, Michael T ; Wu, Tzyy Choou ; Hung, Chien-Fu ; Hanes, Justin S. / Vaginal Delivery of Paclitaxel via Nanoparticles with Non-Mucoadhesive Surfaces Suppresses Cervical Tumor Growth. In: Advanced healthcare materials. 2014 ; Vol. 3, No. 7. pp. 1044-1052.
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AU - Zeng, Qi

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AU - Simons, Brian W.

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AU - Juang, Chih Yin

AU - Mert, Olcay

AU - Wood, Joseph

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AU - Mcmahon, Michael T

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