Research ArticleNanomedicine

Mucus-Penetrating Nanoparticles for Vaginal Drug Delivery Protect Against Herpes Simplex Virus

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Science Translational Medicine  13 Jun 2012:
Vol. 4, Issue 138, pp. 138ra79
DOI: 10.1126/scitranslmed.3003453

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Thick and Sticky

For most, mucus is an unfortunate, never-ending by-product of a summer cold. For those in nanomedicine, however, mucus represents a formidable barrier to delivering drugs to various tissues, including the sinuses and the vagina. Here, Ensign and colleagues have devised a nanoparticle that is capable of penetrating the thick mucus layer standing between drug and tissue of interest.

To develop a drug delivery vehicle that could not only move through mucus, but also afford sustained release over time, Ensign et al. coated polystyrene or biodegradable poly(lactic-co-glycolic acid) nanoparticles with a low–molecular weight polymer commonly known as PEG. These mucus-penetrating particles (MPPs) moved quickly through mouse cervicovaginal mucus (CVM) when delivered in hypotonic solution, allowing them to penetrate deep into the vaginal folds within minutes and to remain there for 24 hours. Conversely, conventional, uncoated particles were stuck in the thick mucus layer, unable to reach the tissue below. Both particle types displayed the same behavior in human CVM ex vivo.

Ensign et al. showed that these particles could protect against vaginal transmission of herpes simplex virus (HSV). Mice were administered either MPPs laden with a modified form of the drug acyclovir—which is used in humans to treat HSV outbreaks—or a soluble form of the drug, before challenge with the virus. Of the mice that received the MPPs, only 47% of the mice were infected with HSV, whereas 84% of the controls were infected after receiving soluble acyclovir at the same concentration. Although more tests will be needed to show protection against herpes in situations that more closely mimic the human vagina, these MPPs may be the key to safe and effective drug delivery to prevent and treat sexually transmitted infections.