The ability to control would contraction is important in preventing disfiguring scarring in burn and trauma patients. Fibroblasts within the wound generate the mechanical forces that cause this contraction, and their interactions with various extracellular matrix components are thought to regulate this process. Rhamnolipids inhibit DNA synthesis and proliferation of different cell types including keratinocytes and fibroblasts both in vitro and in vivo. The drug is more effective in its inhibition of fibroblasts, ordinarily faster growing cells. Therefore, healing of wounds treated with rhamnolipd(s) would be somewhat slowed. During Phase I, we will determine the optimal concentration of rhamnolipid for topical treatment of wounds, to enable healing without contraction.. This will be accomplished assaying the drug in 2 in vitro would healing assays: fibroblast populated collagen lattice contraction assay, and the wounded monolayer assay for keratincyte migration. The drug will also be assayed in an in vivo rat burn would model. In addition, Phase I will allow the company to identify commercial suppliers and establish the cost effectiveness of the drug as compared to conventional treatments. Phase II efforts will then be directed at human trials at two multicenter facilities. Laboratory scale fermentation and purification of rhamnolipids or synthesis facilities will need to be developed to produce the compound for human trials in Phase II.
There are no drugs which can prevent contractures in healing burn or other wounds. Wound healing without contracture is one of the very important tasks in surgery. Aside from the cosmetic and functional value, this drug may be so important in abdominal and pelvic surgeries. Fibrous tissue formation could lead to death in these cases, because to ileus. Drugs capable to reduce scar formation have enormous market value.
|Stipcevic, Tamara; Piljac, Ante; Piljac, Goran (2006) Enhanced healing of full-thickness burn wounds using di-rhamnolipid. Burns 32:24-34|
|Stipcevic, Tamara; Piljac, Tihana; Isseroff, Roslyn R (2005) Di-rhamnolipid from Pseudomonas aeruginosa displays differential effects on human keratinocyte and fibroblast cultures. J Dermatol Sci 40:141-3|