Treatment With a Novel Topical Nanoemulsion (NB-001) Speeds Time to Healing of Recurrent Cold Sores
August 2012 | Volume 11 | Issue 8 | Original Article | 970 | Copyright © August 2012
Leon Kircik MD,a* Terry M. Jones MD,b* Michael Jarratt MD,c* Mary R. Flack MD,d Marian Ijzerman PhD,d Susan Ciotti PhD,d Joyce Sutcliffe PhD,d Guy Boivin MD,e Lawrence R. Stanberry MD PhD,f and James R. Baker MDg* for the NB-001 Study Group
aPhysicians Skin Care, PLLC, Louisville, KY, Mount Sinai Medical Center, New York, NY, and Indiana University School of Medicine, Indianapolis, IN bJ&S Studies, Inc., College Station, TX; cDermResearch, Inc., Austin, TX dNanoBio Corporation, Ann Arbor, MI eCentre Hospitalier Universitaire de Québec, Quebec, Canada fColumbia University College of Physicians and Surgeons, New York, NY gUniversity of Michigan, Ann Arbor, MI
Abstract
Background: Current topical therapies for cold sores are only marginally beneficial due to poor skin penetration. We assessed the safety and efficacy of a novel topical antiviral nanoemulsion (NB-001) with high tissue bioavailability.
Objectives: The primary endpoint was the time to lesion healing.
Methods: 482 subjects with recurrent cold sores were randomized to self-initiate treatment with either vehicle or NB-001 (0.1%, 0.3% or 0.5%) at the first signs or symptoms of a cold sore episode. Lotion was applied 5 times per day, approximately 3 to 4 hours apart, for 4 days. Time to lesion healing was correlated with NB-001 bioavailability determined in human cadaver skin.
Results: Subjects treated with 0.3% NB-001 showed a 1.3-day improvement in the mean time to healing compared to vehicle (P=0.006). This was consistent with human cadaver skin data indicating that the 0.3% nanoemulsion had the highest bioavailability, compared to 0.1% and 0.5% emulsions. No significant safety or dermal irritation concerns or systemic absorption were noted with any of the doses.
Conclusions: Topical NB-001 (0.3%) was well tolerated and highly efficacious in shortening the time to healing of cold sores. The improvement in time to healing was similar to that reported for oral nucleoside analogues, but without systemic exposure. Topical agents for recurrent herpes labialis (cold sores) reduce healing time by one half day, compared to oral therapies that speed healing by a day or more. A topical antiviral nanoemulsion was well tolerated and improved cold sore healing time by over a day compared to vehicle control. Nanoemulsion (NB-001) could represent a more efficacious topical treatment for recurrent cold sores.
J Drugs Dermatol. 2012;11(8):970-977.
INTRODUCTION
Herpes labialis is an exceedingly common condition caused by episodic reactivation of latent herpes simplex
virus, type 1 (HSV-1) leading to recurrent painful and socially embarrassing lesions (cold sores).1-5 Up to 90% of adults have been exposed to HSV-1 and harbor latent virus in their trigeminal ganglia,5,6 one-third of whom experience viral reactivation in response to factors such as fever, stress, or ultraviolet
light.1-4 Following reactivation, the virus travels down the trigeminal ganglia, exits nerve endings in the lips and causes a cold sore blister.6 Oral nucleoside analogues are effective if given early in high doses,7-12 but are limited to prescription use in the US due to concerns about the development of drug resistance.13 The currently available topical agents are only marginally effective
due to their relative inability to reach the site of infection.14-16
NB-001 is a novel, topical, oil-in-water emulsion with nanometer-
sized droplets composed of pharmaceutically approved ingredients including soybean oil, poloxymer 20, and the cationic
surfactant cetylpyridinium chloride (CPC).17,18 The surfactants on the surface of the droplets prevent them from coalescing in solution (Figure 1). When applied to the skin, however, the droplets
undergo transfollicular migration to the dermal-epidermal junction, where the herpes virus exits the nerve ending.19,21 The droplets are thermodynamically driven to fuse with and disrupt the viral envelope (Figure 2a) leading to potent in vitro activity against HSV-1, including thymidine kinase resistant isolates (Figure
2b). Topical application of NB-001 to mice inoculated with a lethal dose of HSV-1 reduced lesion formation and promoted survival similar to intraperitoneal acylovir (Figure 2c).
A previous study of NB-001 in 332 subjects with recurrent cold sores demonstrated no skin irritation, safety concerns, or systemic
absorption, and about half a day shortening of time to healing for the highest dose studied (0.1% NB-001) compared
