title: Pretreatment of human cervicovaginal mucus with pluronic F127 enhances nanoparticle penetration without compromising mucus barrier properties to herpes simplex virus.
abstract: Mucosal drug delivery nanotechnologies are limited by the mucus barrier that protects nearly all epithelial surfaces not covered with skin. Most polymeric nanoparticles, including polystyrene nanoparticles (PS), strongly adhere to mucus, thereby limiting penetration and facilitating rapid clearance from the body. Here, we demonstrate that PS rapidly penetrate human cervicovaginal mucus (CVM), if the CVM has been pretreated with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large polyethylene glycol (PEG)-coated, nonmucoadhesive nanoparticles (PS-PEG) did not change in F127-pretreated CVM, implying that F127 did not significantly alter the native pore structure of CVM. Additionally, herpes simplex virus type 1 (HSV-1) remains adherent in F127-pretreated CVM, indicating that the presence of F127 did not reduce adhesive interactions between CVM and the virions. In contrast to treatment with a surfactant that has been approved for vaginal use as a spermicide (nonoxynol-9 or N9), there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for 1 week. Pluronic F127 pretreatment holds potential as a method to safely improve the distribution, retention, and efficacy of nanoparticle formulations without compromising CVM barrier properties to pathogens.
authors.affiliation: Center for Nanomedicine, ‡Department of Ophthalmology, The Wilmer Eye Institute, ⊥Department of Biomedical Engineering, and ○Departments of Neurosurgery and Oncology, Johns Hopkins University, School of Medicine , Baltimore, Maryland, United States.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Ensign
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Lai
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Olcay
authors.initials: O
authors.lastname: Mert
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
authors.forename: Richard
authors.initials: R
authors.lastname: Cone
mesh_terms: D000818:Animals; D002582:Cervix Mucus / Q000187:drug effects* / Q000821:virology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology; D017137:Nonoxynol / Q000494:pharmacology; D020442:Poloxamer / Q000737:chemistry / Q000494:pharmacology*; D018139:Simplexvirus / Q000472:pathogenicity; D013501:Surface-Active Agents / Q000494:pharmacology; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*
chemical_list: D004337:Drug Carriers; D013501:Surface-Active Agents; D020442:Poloxamer; D017137:Nonoxynol