Enhancement effect of terpenes on silver sulphadiazine permeation through third-degree burn eschar

Antimicrobial therapy remains one of the most important methods of wound management. Systemically administered antimicrobials may not achieve therapeutic levels in wound and most agents cannot penetrate burn eschar well enough when applied topically. Therefore, we tested the notion to increase permeability of eschar toward topical agents using terpenes, a well-known class of skin permeation enhancers. Four terpenes, limonene (hydrocarbon), eucalyptol (ether), alpha-pinene oxide (epoxide) and geraniol (alcohol) were chosen and their effects on permeation of silver sulphadiazine (SSD), a widely used topical antimicrobial agent, through human third-degree burn eschar was evaluated using static diffusion cells. Results showed that terpenes increased permeation flux of SSD through eschar significantly (P<0.0001). Limonene provided the highest flux enhancement ratio (9.0 times), followed by geraniol, eucalyptol and alpha-pinene oxide with enhancement ratios of 5.5, 4.7 and 4.3 respectively. The effects of terpenes on permeation lag-time, was less than 20%. Data analysis revealed that terpenes increase permeation of SSD mainly by increasing its partitioning into the eschar. The present results show that permeation of drugs through burn eschar can be increased considerably by terpenes and that burn wound antimicrobial therapy may be improved by terpenes and possibly other penetration enhancers.