Heparin penetration into and permeation through human skin from aqueous and liposomal formulations in vitro

The transport of unfractionated (UH) and low molecular weight Heparin (LMWH) in human skin was investigated in vitro using heat separated epidermal membrane and dermis and the effect of liposomal formulations with Phospholipon(R) 80 (PL80) and Sphingomyelin (SM) was assessed, The distribution or Heparin within skin tissue was studied by the tape stripping method. Heparin concentrations were measured with a biological assay. Transepidermal water loss was determined to characterize barrier properties of skin. No consistent permeation of Heparin through epidermal membrane was detected. Penetration into the epidermal membrane was for LMWH significantly greater than for UH, Accumulation of UH was largely restricted to the outermost layers of the stratum corneum while LMWH penetrated into deeper epidermal layers. UH penetration into epidermis was detected for the PL80 liposomal formulation only. The extent of LMWH penetration was independent of the formulation, LMWH, however, showed a trend to accumulate in deeper epidermal layers for the PL80 compared to the aqueous formulation. Thus, molecular weight and liposomal formulations influenced the penetration pattern of Heparin in the epidermis. It can not be concluded whether the concentration of LMWH achieved at the blood capillaries is sufficient to exert a phamacological effect. UH permeated readily through dermis irrespectively of formulation and its accumulation in the dermis was significantly enhanced and its lag time of permeation increased in the presence of SM liposomes. (C) 2001 Elsevier Science B.V. All rights reserved.