Comparison of different membranes with cultures of keratinocytes from man for percutaneous absorption of nitroglycerine.
The permeability barrier function of cell-culture membranes to the permeation of nitroglycerine was evaluated to find an alternative to skin from man for ex-vivo skin-permeation tests. The membranes were prepared, under submerged conditions, by inducing the growth of keratinocytes, from different donors, on a film of esterified jaluronic acid for different times (10, 20 and 30 days). Their permeability barrier functions were compared with those of some of the most widely used artificial membranes, silicone rubber (Silastic), cellulosic material (Cuprophan, Millipore HAWP), polysulphone membrane (Supor) and polytetrafluoroethylene membrane (TF-PTFE), and with those of biological membranes such as fresh and frozen skin, stratum corneum and epidermis from man, and hairless mouse skin. For each membrane the permeation profile was obtained and the flux was calculated. The permeation profiles for nitroglycerine were similar and linear in the first 2-3 h for all the synthetic membranes tested except TF-PTFE. For this membrane the profile was linear throughout the period considered and the amount permeating in 24 h (1603 microg cm(-2)) was significantly lower than those obtained for the other artificial membranes (between 1926 and 2508 microg cm(-2)). The amounts permeating through all the biological membranes in 24 h were in the range 520 to 781 microg cm(-2), except those for the keratinocyte-culture membranes, which were in the range 1730 to 2553 microg cm(-2). Prolonging the growth period of cultured keratinocytes did not affect nitroglycerine permeation. The findings suggest that these keratinocyte-culture membranes have some advantages--good reproducibility if obtained from the same donor; many membranes can be obtained from the same donor; the preparation is simple; they can be handled more easily than traditional cell-culture membranes; and they afford constant penetration rates for a longer period than synthetic membranes. The membranes could be used for preliminary in-vitro permeation studies.
Minghetti
P
P
Istituto di Chimica Farmaceutica e Tossicologica, Milano, Italy.
Casiraghi
A
A
Cilurzo
F
F
Montanari
L
L
Marazzi
M
M
Falcone
L
L
Donati
V
V
D000818:Animals; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D005996:Nitroglycerin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption; D012995:Solubility; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
D014665:Vasodilator Agents; D005996:Nitroglycerin