Abstract
Original language | English |
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Pages (from-to) | 631-640 |
Number of pages | 10 |
Journal | British Journal of Dermatology |
Volume | 123 |
Issue number | 5 |
DOIs | |
Publication status | Published - 1 Nov 1990 |
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Keywords
- Animals
- Azepines
- Cyclosporins
- Guinea Pigs
- Humans
- Hypersensitivity, Delayed
- Leukocyte Count
- Male
- Propylene Glycols
- Skin
- Skin Absorption
- T-Lymphocytes, Cytotoxic
- T-Lymphocytes, Regulatory
- Time Factors
- Vehicles
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Enhanced percutaneous absorption of a novel topical cyclosporin A formulation and assessment of its immunosuppressive activity. / Duncan, J I; Payne, S N; Winfield, A J; Ormerod, Anthony; Thomson, A W.
In: British Journal of Dermatology, Vol. 123, No. 5, 01.11.1990, p. 631-640.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Enhanced percutaneous absorption of a novel topical cyclosporin A formulation and assessment of its immunosuppressive activity
AU - Duncan, J I
AU - Payne, S N
AU - Winfield, A J
AU - Ormerod, Anthony
AU - Thomson, A W
PY - 1990/11/1
Y1 - 1990/11/1
N2 - No clinically successful topical cyclosporin A (CyA) formulation has been produced, mainly due to the apparent lack of drug penetration. This study has produced the first in vitro kinetic data on CyA penetration across human cadaver stratum corneum and has shown that addition of the penetration enhancers (PE) Azone and propylene glycol to the CyA vehicle significantly enhanced drug permeation across the skin barrier. Using flow-through permeability cells with 5% w/v CyA (Sandimmun) alone (CyA) or with PE (CyA + PE) in olive oil in the donor chamber, the penetration rate (mean +/- SD microgram/cm2/h) into receptor fluid was 53 +/- 43 (n = 13) for CyA and 660 +/- 175 (n = 7) for CyA + PE. The in vivo efficacy of this formulation was assessed in guinea-pigs undergoing delayed-type hypersensitivity (DTH) reactions to dinitrofluorobenzene (DNFB). CyA was applied topically at the time of challenge and twice daily thereafter. At 24 h, skin reactions revealed that compared with appropriate drug vehicles, concentrations of 0.25, 0.5 and 5% CyA +/- PE had a significant inhibitory effect upon the erythema response and this corresponded with significant reductions in T-cell infiltrates (0.5 and 5% CyA). No statistically significant reductions in erythema were demonstrated with 0.05% CyA +/- PE, but there was a reduction in the number of infiltrating lymphocytes in sites receiving 0.05% CyA + PE compared with vehicle-treated sites (P less than 0.01). This suggests that PE permitted some penetration of an otherwise non-immunosuppressive concentration of CyA through the skin.
AB - No clinically successful topical cyclosporin A (CyA) formulation has been produced, mainly due to the apparent lack of drug penetration. This study has produced the first in vitro kinetic data on CyA penetration across human cadaver stratum corneum and has shown that addition of the penetration enhancers (PE) Azone and propylene glycol to the CyA vehicle significantly enhanced drug permeation across the skin barrier. Using flow-through permeability cells with 5% w/v CyA (Sandimmun) alone (CyA) or with PE (CyA + PE) in olive oil in the donor chamber, the penetration rate (mean +/- SD microgram/cm2/h) into receptor fluid was 53 +/- 43 (n = 13) for CyA and 660 +/- 175 (n = 7) for CyA + PE. The in vivo efficacy of this formulation was assessed in guinea-pigs undergoing delayed-type hypersensitivity (DTH) reactions to dinitrofluorobenzene (DNFB). CyA was applied topically at the time of challenge and twice daily thereafter. At 24 h, skin reactions revealed that compared with appropriate drug vehicles, concentrations of 0.25, 0.5 and 5% CyA +/- PE had a significant inhibitory effect upon the erythema response and this corresponded with significant reductions in T-cell infiltrates (0.5 and 5% CyA). No statistically significant reductions in erythema were demonstrated with 0.05% CyA +/- PE, but there was a reduction in the number of infiltrating lymphocytes in sites receiving 0.05% CyA + PE compared with vehicle-treated sites (P less than 0.01). This suggests that PE permitted some penetration of an otherwise non-immunosuppressive concentration of CyA through the skin.
KW - Animals
KW - Azepines
KW - Cyclosporins
KW - Guinea Pigs
KW - Humans
KW - Hypersensitivity, Delayed
KW - Leukocyte Count
KW - Male
KW - Propylene Glycols
KW - Skin
KW - Skin Absorption
KW - T-Lymphocytes, Cytotoxic
KW - T-Lymphocytes, Regulatory
KW - Time Factors
KW - Vehicles
U2 - 10.1111/j.1365-2133.1990.tb01480.x
DO - 10.1111/j.1365-2133.1990.tb01480.x
M3 - Article
VL - 123
SP - 631
EP - 640
JO - British Journal of Dermatology
JF - British Journal of Dermatology
SN - 0007-0963
IS - 5
ER -