Port Wine Stain Study

Conrex Pharmaceutical Corporation joined with Beckman Laser Institute; Department of Biomedical Engineering – University of California, Irvine; Edwards Lifesciences Center for Advanced Cardiovascular Technology – UCI; Department of Dermatopathology, Massachusetts General Hospital, Harvard Medical School; and Department of Pathology, Baylor College of Medicine, Houston, Texas to study how PET™ could be an effective vehicle to deliver RPM in to the dermis in conjunction with laser therapy to inhibit PWS.

Background and Objectives:

Complete blanching of port wine stain (PWS) birthmarks after laser therapy is rarely achieved for most patients. We postulate that the low therapeutic efficacy or treatment failure is caused by regeneration and revascularization of photocoagulated blood vessels due to angiogenesis associated with the skin’s normal wound healing response. Rapamycin (RPM), an antiangiogenic agent, has been demonstrated to inhibit growth of pathological blood vessels. Our objectives were to
(1) investigate whether topical RPMcan inhibit reperfusion of photocoagulated blood vessels in an animal model and
(2) determine the effective RPM concentration required to achieve this objective.

Study Design/Materials and Methods:

For both laseronly and combined laser and RPM treated animals, blood vessels in the dorsal window chambers implanted on golden Syrian hamsters were photocoagulated with laser pulses. Structural and flow dynamics of blood vessels were documented with color digital photography and laser speckle imaging to evaluate photocoagulation and reperfusion. For the combined treatment group, topical RPM was applied to the epidermal side of the window daily for 14 days after laser exposure.

Results:

In the laser-only group, 23 out of 24 photocoagulated blood vessels reperfused within 5–14 days. In the combined treatment group with different RPM formulae and concentrations, the overall reperfusion rate of 36% was much lower as compared to the laser-only group.
We also found that the reperfusion rate was not linearly proportional to the RPM concentration.

Conclusions:

With topical RPM application, the frequency of vessel reperfusion was considerably reduced, which implies that combined light and topical antiangiogenic therapy might be a promising approach to improve the treatment efficacy of PWS birthmarks

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The advantage of topical application is that RPM could be delivered to the dermis while avoiding significant systemic drug absorption and associated side effects [41]. Two different topical RPM formulae were tested in this study. In both formulae, a skin penetration enhancer (PET™) was used. The results indicate that RPM can be effectively delivered through the stratum corneum using this enhancer.