The Potential of a Site-Specific Delivery of Thiamine Hydrochloride as a Novel Insect Repellent Exerting Long-Term Protection on Human Skin: In-vitro, Ex-vivo Study and Clinical Assessment.

Abstract

Thiamine hydrochloride (TH) was thought to exert a good insect repellent activity. The purpose of this work was to develop a formulation that releases TH in sustained regimen on human skin. Long lasting protection against mosquito bites was achieved. Pullulan acetate (PA) was used to prepare TH nanospheres. Optimal system was incorporated in Pluronic® hydrogel. Formulae were tested for in-vitro release and ex-vivo permeation. Complete protection time (CPT) was done adopting Kaplan-Meier survival function for the synthetic repellent (DEET), TH solution and nanospheres in hydrogel. Release profile of TH solution, nanospheres and nanosphere-loaded hydrogel (DG) demonstrated an added effect of DG, where t 1/2 was 11.2±1.4h. SEM for DG showed homogenous dispersion of nanospheres inside the matrix of the gel. Ex-vivo permeation showed only 0.761 ± 0.04% of TH in hydrogel permeated the skin after 12h, while 44.98 ± 3.2% permeated when TH solution was applied. Clinical study revealed a significant difference in CPT between TH solution with either DEET or (DG) (p<0.05), and no significant difference between DEET and DG with CPT 400 ± 31 and 360 ± 18min, respectively (P > 0.05). The high efficacy of TH-loaded hydrogel rendered it a successful alternative for DEET, offering long protection against mosquito bites.