Enhanced topical delivery and ex vivo anti-inflammatory activity from a betamethasone dipropionate formulation containing fish oil.
OBJECTIVE
To probe ex vivo the influence of fish oil (FO) on the topical delivery and anti-inflammatory properties of betamethasone dipropionate (BD).


METHODS
Freshly excised porcine ear skin.


METHODS
Ointment formulations containing BD + salicylic acid (SA), BD + SA + FO, or base as control, applied to the skin mounted in Franz cells.


METHODS
Comparative depth profiling; skin probed by immunohistochemistry for cyclooxygenase-2 (COX-2) and by ELISA for prostaglandin E2 (PGE2).


RESULTS
More BD was obtained in the first 30 layers and the remaining epidermis with BD + SA. However, more penetrants were recovered from the remaining skin treated with BD + SA + FO. Although BD + SA reduced COX-2 expression within the epidermis, greater reduction was observed with BD + SA + FO as indicated by reduced COX-2 expression. FO alone had a comparable effect on the expression of COX-2. Modulation of PGE2 production also supported the anti-inflammatory properties of fish oil, reducing PGE2 levels by an amount comparable to the reduction by BD. Combining FO and BD, however, did not provide the anticipated potentiation effect.


CONCLUSIONS
Fish oil enhanced the delivery of BD and SA across skin. Addition of fish oil also enhanced the anti-inflammatory activity of BD, attributed to increased amounts of BD present in the skin and/or the intrinsic anti-inflammatory activity of fish oil.
Zulfakar
Mohd Hanif
MH
Cardiff University, UK.
Abdelouahab
Nassima
N
Heard
Charles M
CM
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004359:Drug Therapy, Combination; D005395:Fish Oils / Q000008:administration & dosage / Q000493:pharmacokinetics*; D023421:Models, Animal; D020156:Salicylic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology*; D013552:Swine
D000893:Anti-Inflammatory Agents; D005395:Fish Oils; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D020156:Salicylic Acid