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 of 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 pharmacological 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.
Betz
G
G
Institute of Pharmaceutical Technology, Department of Pharmacy, University of Basel, Klingelbergstr. 50, 4056, Basel, Switzerland.
Nowbakht
P
P
Imboden
R
R
Imanidis
G
G
D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D019999:Pharmaceutical Solutions; D012869:Skin Absorption; D014870:Water Loss, Insensible
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008081:Liposomes; D019999:Pharmaceutical Solutions; D006493:Heparin