Microemulsion-based oxyresveratrol for topical treatment of herpes simplex virus (HSV) infection: physicochemical properties and efficacy in cutaneous HSV-1 infection in mice

Abstract

The physicochemical properties of the optimized microemulsion and the permeating ability of oxyresveratrol in microemulsion were evaluated, and the efficacy of oxyresveratrol microemulsion in cutaneous herpes simplex virus type 1 (HSV-1) infection in mice was examined. The optimized microemulsion was composed of 10% w/w of isopropyl myristate, 35% w/w of Tween 80, 35% w/w of isopropyl alcohol, and 20% w/w of water. The mean particle diameter was 9.67 ± 0.58 nm, and the solubility of oxyresveratrol in the microemulsion was 196.34 ± 0.80 mg/ml. After accelerated and long-term stability testing, the microemulsion base and oxyresveratrol-loaded microemulsion were stable. The cumulative amount of oxyresveratrol permeating through shed snake skin from microemulsion at 6 h was 93.04 times compared to that of oxyresveratrol from Vaseline, determined at 20% w/w concentration. In cutaneous HSV-1 infection in mice, oxyresveratrol microemulsion at 20%, 25%, and 30% w/w, topically applied five times daily for 7 days after infection, was significantly effective in delaying the development of skin lesions and protecting from death (p < 0.05) compared with the untreated control. Oxyresveratrol microemulsion at 25% and 30% w/w was significantly more effective than that of 30% w/w of oxyresveratrol in Vaseline (p < 0.05) and was as effective as 5% w/w of acyclovir cream, topically applied five times daily (p > 0.05). These results demonstrated that topical oxyresveratrol microemulsion at 20-30% w/w was suitable for cutaneous HSV-1 mouse infection.

Fig. 1

Pseudoternary phase diagram of isopropyl myristate/Tween80/isopropanol/water system at 1:1 (a), 2:1 (b), and 4:1 (c) w/w ratio of surfactant and cosurfactant

Fig. 2

In vitro permeation of oxyresveratrol in microemulsion in shed snake skin (mean ± SD, n = 3)

Fig. 3

Concentration-dependent efficacy of oxyresveratrol microemulsion in cutaneous HSV-1 infection in mice observed at day 5 after infection. These results were part of the same experiment as that of Table V (data represented the mean ± SE and were determined from nine to ten mice in each group)