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WIREs Nanomed Nanobiotechnol
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Mucoadhesive nanosystems for vaginal microbicide development: friend or foe?

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Abstract Topical microbicides are a promising strategy in the prevention of vaginal and rectal HIV transmission as well as other sexually transmitted pathogens. The perspective of developing nanotechnology‐based systems for topical microbicides seems to be useful because important features such as enhanced drug release, targeting, and epithelial penetration can be achieved. However, the interaction of nanoparticles with the mucus fluids that cover the cervicovaginal mucosal epithelium, which can work either as a docking point or as a barrier for diffusion, has been frequently neglected. In this review, we discuss the principles of nanosystems' adhesion to the mucosal tissue and how this relates to the development of optimized microbicide formulations. WIREs Nanomed Nanobiotechnol 2011 3 389–399 DOI: 10.1002/wnan.144 This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Schematic representation of the relative ability of particles to diffuse through mucus, considering its size and surface properties (i.e., engineered to interact or not with mucin).

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Transport of poly(sebacic acid)–polyethylene glycol (PSA–PEG) and poly(sebacic acid) (PSA) nanoparticles in human cervicovaginal mucus showing reduced diffusion impairment after PEG modification. (a) Fluorescent image showing a dense PEG coating (biotin‐functionalized PEG) on a PSA–PEG particle (scale bar = 50 nm). Representative 20‐second diffusion trajectories of (b) PSA and (c) PSA–PEG nanoparticles in mucus. (d) Ensemble‐averaged geometric mean‐squared displacements (<MSD>) for PSA and PSA–PEG nanoparticles as a function of time scale. Data represent the ensemble average of three independent experiments, with n ≥ 150 different particle trajectories for each experiment. Error bars indicate standard error. * denotes statistically significant difference compared with PSA nanoparticles (one‐tailed, unequal variance Student's t‐test; p < 0.05). (Reprinted with permission from Ref 53. Copyright 2009 The National Academy of Sciences, USA)

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Summary of used strategies for engineering the mucoadhesive behavior of nanosystems.

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Typical network‐shaped mesh of cervical mucus around ovulation, with pores measuring 3–4 µm in diameter in the more compact areas and 5–10 µm in the laxer areas (bar = 20 µm). (Reprinted with permission from Ref 46. Copyright 2005 Oxford University Press and The Japanese Society of Microscopy)

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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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