Nanoparticle penetration of human cervicovaginal mucus: The effect of polyvinyl alcohol

Abstract

Therapeutic nanoparticles must rapidly penetrate the mucus secretions lining the surfaces of the respiratory, gastrointestinal and cervicovaginal tracts to efficiently reach the underlying tissues. Whereas most polymeric nanoparticles are highly mucoadhesive, we previously discovered that a dense layer of low MW polyethylene glycol (PEG) conferred a sufficiently hydrophilic and uncharged surface to effectively minimize mucin-nanoparticle adhesive interactions, allowing well-coated particles to rapidly diffuse through human mucus. Here, we sought to investigate the influence of surface coating by polyvinyl alcohol (PVA), a relatively hydrophilic and uncharged polymer routinely used as a surfactant to formulate drug carriers, on the transport of nanoparticles in fresh human cervicovaginal mucus. We found that PVA-coated polystyrene (PS) particles were immobilized, with speeds at least 4,000-fold lower in mucus than in water, regardless of the PVA molecular weight or incubation concentration tested. Nanoparticles composed of poly(lactide-co-glycolide) (PLGA) or diblock copolymers of PEG-PLGA were similarly immobilized when coated with PVA (slowed 29,000- and 2,500-fold, respectively). PVA coatings could not be adequately removed upon washing, and the residual PVA prevented sufficient coating with Pluronic F127 capable of reducing particle mucoadhesion. In contrast to PVA-coated particles, the similar sized PEG-coated formulations were slowed only ~6- to 10-fold in mucus compared to in water. Our results suggest incorporating PVA in the particle formulation process may lead to the formation of mucoadhesive particles for many nanoparticulate systems. Thus, alternative methods for particle formulation, based on novel surfactants or changes in the formulation process, should be identified and developed in order to produce mucus-penetrating particles for mucosal applications.

Development and Characterization of Piper Retrofractum Extract Loaded Mucoadhesive Nanostructured Lipid Carriers for Topical Oral Drug Delivery

“…The particle size and the nature of coated polymer are the main parameters affecting mucoadhesive potential. In general, the mucosa tissue is coated with a mucus gel layer composed of glycoprotein fibers mesh that could physically trap small particle sizes of<200 nm [18,19]. As a consequence, the uncoated-NLCs with mean particle size ~ 100 nm could be immobilized within the mucus layer, and thus, avoid elimination by the fluid flow.…”

Development and Characterization of Nisin Nanoparticles as Potential Alternative for the Recurrent Vaginal Candidiasis Treatment

“…In addition, one particularly important characteristic of any novel delivery system destined for topical administration within the vagina is a low propensity to cause genital irritation and systemic toxicity. Thus, drug delivery strategies that enhance the residence (retention) of antifungal drugs at mucosal tissues while reducing systemic exposure may be interesting toward the development of vaginal microbicides (29)(30)(31)(32)(33). Ideally, NIS-NP should have its size adjusted near to 300 nm, in order to enable its penetration into a vaginal mucosa cells, forming a NIS reservoir system, which would be helpful for prevention of C. albicans uncontrolled proliferation (34).…”

The Ins and Outs of Nanoparticle Technology in Neurodegenerative Diseases and Cancer

“…Following from that, whatever the administration route, nature, composition and building of the NP should be highly studied. The majority of the targeted ways (eyes, nose, lungs, gastrointestinal tract, cervico-vaginal) involves the crossing of a mucus barrier before internalisation of the NPs by the cells [82,83]. In the case of local administration into the nose or the eyes, for example, the mucoadhesive properties of the NP must be high enough to enhance the retention time in the aim to extend the time of contact with the biological membranes to improve the drug absorption [84].…”