Effect Of Low Molecular Weight Heparin Through Percutaneous Permeation On Survival Of Random Skin Flaps

Objective: To investigate the influence of two different chemical enhancers on low molecular weight heparin through percutaneous penetration and to develop suitable formulations of LMWH gel, then to evaluate the effects of the LMWH gel on rat dorsal ischemic skin flaps.Methods: 100IU/g, 200IU/g, 300IU/g, 400IU/g, 500IU/g of LMWH gels with two different enhancers containing 3%Azone and 5%NMP, and 3%Azone+5%NMP were made. Skin permeation experiment was completed with a modified Franz's diffusion cell in vitro. The quantum of accumulative penetration (IU/cm~2) of LMWH gel across mouse and rat skin for 1, 2,3,5,8,12h was tested. To evaluate whether the LMWH gel improve skin flap survival in rats, random skin flaps were raised in 15 Wistar rats. 300IU/g and 500IU/g LMWH gel (n=5) or controlled gel (n=5) were administered 1g/24h after flap elevation. Surviving flap areas were measured after 7 days.Results: 1. LMWH could permeate through the skin of mouse and rat. Concentrations of LMWH within skin in the blends of containing 3%Azone and 5%NMP is higher than in 3%Azone or 5%NMP(P＜0.05).2. The mean surviving flap area in the 300IU/g LMWH was greater than that in controlled and 500IU/g LMWH (P＜0.05).Conclusion: 1. LMWH could permeate the skin of mouse and rat. The quantum of accumulative penetration (IU/cm~2) of LMWH in the skin might depend on the concentration of LMWH gels. The promoting effect of blends of containing 3%Azone and 5%NMP had a satisfactory percutaneous permeability.2. 300IU/g of LMWH gel through percutaneous penetration could improve of survivals of the ischemic rat skin flap.