Reduction of skin flap necrosis by transdermal application of buflomedil bound to liposomes

The influence of the vasoactive drug buflomedil hydrochloride bound to liposomes (2 mg/ml) was investigated in an arterial pattern skin flap model using the ear of hairless mice. For flap creation, the ear is cut at four-fifths ofits base which leaves the anterior artery as the only feeding vessel of the flap. Liposomes were locally applied daily for 30 minutes up to 5 days after flap creation. Microvascular perfusion in the proximal, central, and distal parts of the flap was measured by laser Doppler flow-metry. The border between perfused and nonperfused tissue was visualized by intravital fluorescence microscopy using fluorescein isothiocyanate (FITC)-labeled dextran (M, 150,000) for contrast enhancement of microvessels. The area of nonperfused tissue was assessed by digital planimetr Five days after flap creation the nonperfused area amounted to 23.8 ± 3.1 percent of total flap surface in treated ears compared with 46.1 ± 5.6 percent in untreated ears (p < 0.05) of the contralateral side. Additional preoperative treatment for 5 days did not further reduce the area of nonperfused tissue (treated ears, 23.0 ± 1.3 percent; control ears, 44.6 ± 5.1 percent). Microvascular perfusion was higher in the postoperatively treated ears in all parts of the flap from day I after flap creation until termination of the experiment. Five days after flap creation, perfusion as measured by laser Doppler flowmetry was reduced to 46.0 ± 10.8 percent in the distal part in control ears compared with 91.9 ± 8.3 percent (p < 0.05) in treated animals. Additional preoperative treatment for 5 days did not result in further improvement. It is concluded that local application of the vasoactive drug buflomedil docked to liposomes could be of therapeutic use in the treatment of ischemic tissue, including skin flaps.