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 me mbrane and dermis and the effect of liposomal formulations with Phospholipo n(R) 80 (PL80) and Sphingomyelin (SM) was assessed, The distribution or Hep arin within skin tissue was studied by the tape stripping method. Heparin c oncentrations were measured with a biological assay. Transepidermal water l oss was determined to characterize barrier properties of skin. No consisten t permeation of Heparin through epidermal membrane was detected. Penetratio n into the epidermal membrane was for LMWH significantly greater than for U H, Accumulation of UH was largely restricted to the outermost layers of the stratum corneum while LMWH penetrated into deeper epidermal layers. UH pen etration into epidermis was detected for the PL80 liposomal formulation onl y. The extent of LMWH penetration was independent of the formulation, LMWH, however, showed a trend to accumulate in deeper epidermal layers for the P L80 compared to the aqueous formulation. Thus, molecular weight and liposom al formulations influenced the penetration pattern of Heparin in the epider mis. It can not be concluded whether the concentration of LMWH achieved at the blood capillaries is sufficient to exert a phamacological effect. UH pe rmeated readily through dermis irrespectively of formulation and its accumu lation in the dermis was significantly enhanced and its lag time of permeat ion increased in the presence of SM liposomes. (C) 2001 Elsevier Science B. V. All rights reserved.