title: Vaginal delivery of paclitaxel via nanoparticles with non-mucoadhesive surfaces suppresses cervical tumor growth.
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.
authors: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD, 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
authors: Ming
authors: M
authors: Yang
authors: Tao
authors: T
authors: Yu
authors: Ying-Ying
authors: YY
authors: Wang
authors: Samuel K
authors: SK
authors: Lai
authors: Qi
authors: Q
authors: Zeng
authors: Bolong
authors: B
authors: Miao
authors: Benjamin C
authors: BC
authors: Tang
authors: Brian W
authors: BW
authors: Simons
authors: Laura M
authors: LM
authors: Ensign
authors: Guanshu
authors: G
authors: Liu
authors: Kannie W Y
authors: KW
authors: Chan
authors: Chih-Yin
authors: CY
authors: Juang
authors: Olcay
authors: O
authors: Mert
authors: Joseph
authors: J
authors: Wood
authors: Jie
authors: J
authors: Fu
authors: Michael T
authors: MT
authors: McMahon
authors: T-C
authors: TC
authors: Wu
authors: Chien-Fu
authors: CF
authors: Hung
authors: Justin
authors: J
authors: Hanes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D051379:Mice; D009093:Mucus / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D013499:Surface Properties; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D014621:Vagina / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel
keywords: biodegradable polymers; cancer; chemotherapy; controlled release; drug delivery