526 Wound Healing Following Electroporation Therapy in a Porcine Model.

Abstract

Currently one of the greatest obstacles facing effective anticancer molecular therapies is efficient drug delivery. Advanced methods such as carriers, liposomes, ultrasound, and viruses have generated modest results with unresolved technical, economical, and regulatory problems. Conventional therapies such as radiation and chemotherapy carry a host of undesirable side effects. Electroporation therapy (EPT) is a promising new modality of drug delivery that exploits the physical process of inducing transient permeability in biological membranes in vivo by short pulses of electric fields. The EPT procedure involves injecting a low dose of drug into cancerous tissue followed by inserting a small needle array that delivers a series of short electrical pulses to induce cellular uptake. In clinical studies EPT has been effective in the treatment of subcutaneous solid tumors of the head and neck, as well as other types of solid tumors when applied with the cytotoxin bleomycin. The utility of EPT has not yet been demonstrated as an adjunct to surgical resection as a potential treatment of wound margins with the aim of reducing tumor recurrence rates. To determine the compatibility of bleomycin-EPT with healing of the surgical wound we studied myocutaneous wound healing in a healthy (noncancerous) porcine model. A series of longitudinal incisions were made along the dorsum of pigs to a depth of 5 mm into the muscle. The margins of each incision were either injected with bleomycin, vehicle (saline), or nothing and two groups received bleomycin or saline, respectively, followed by electroporation (EP). One group received transverse incisions, which were treated with bleomycin-EPT. Wounds were allowed to heal for 2, 7, 14, or 21 days prior to sacrifice and specimens of the incision sites, including skin and muscle, were excised for histological examination. Separate full-thickness skin specimens from across the incision sites were excised and tested for mechanical strength. EP alone showed no significant effect on the mechanical strength of healing porcine skin at any time point. Bleomycin, regardless of use of EP, inhibited the early (< 7 days) development of wound strength; this was most likely due to interference in chemotaxis and/or proliferation of cells involved in early wound healing. However, after 14 days, breaking strength was comparable to saline injected controls. Wound strength after treatment with bleomycin-EPT was higher for longitudinal incisions than for transverse incisions. Histological data documenting the healing process for skin and muscle during the 3 weeks following incision and treatment will be presented.