The incidence and prevalence of chronic topical wounds have significant implication on healthcare expenditure. Recent introduction of the first recombinant growth factor (Regranex[R], becaplermin, rhPDGF-BB) gel in the U.S. has improved the prospect for chronic wound treatment. Nevertheless, Regranex[R] has to be applied repeatedly during a prolonged course of treatment. New therapeutic modalities that could minimize the number of applications/interventions required for chronic wound are desirable. Topical gene transfer could circumvent the drawbacks associated with the current PDGF preparation. We have developed a biodegradable Hyaluronic Acid hydrogel film/matrix for delivering plasmid DNA. In this Phase I program, we will initially optimize the in vitro DNA release characteristics of the film and matrix. Thereafter, the longevity of these delivery vehicles for gene transfer will be studied using model fibroblast (CHO) and endothelial (HUVEC) cells. The program will be concluded by defining the longevity of the in vitro PDGF-B gene delivery from these vehicles in inducing cell proliferation. This single application film/matrix DNA sustained delivery system will provide substantially improved prospects for accelerating wound healing by overcoming the disadvantages associate with the current therapeutic modalities.
Chronic wounds causes major disability and have significant socioeconomic impact. Current treatment of chronic topical wounds requires multiple interventions and thus predisposes patients to discomforts, desiccation and infection which are detrimental to wound healing. This Phase I application is to demonstrate the feasibility of using a biodegradable hydrogel as a new sustained delivery therapeutic modality for gene transfer to accelerate the healing of chronic topical wounds, and thereby reduces the required treatment interventions to a minimal. Promising results obtained will expand this study into Phase II (animal studies) and thereafter clinical trial. This could result in a single application therapeutic modality for treating chronic topical wounds.
| Chen, Weiliam (2012) Preparation of hyaluronan-DNA matrices and films. Cold Spring Harb Protoc 2012:1117-20 |
| Kim, Angela; Checkla, Daniel M; Dehazya, Philip et al. (2003) Characterization of DNA-hyaluronan matrix for sustained gene transfer. J Control Release 90:81-95 |
