Pharmacology of RALGA, a mixture of retinaldehyde and glycolic acid.
BACKGROUND
Retinoids and alpha-hydroxy acids (AHAs) are major compounds in topical therapy. They exert distinct but potentially complementary activities. However, their association is limited by their respective irritating potential. Recently, the first association between a retinoid and an AHA has been achieved; this formulation (RALGA) associates retinaldehyde (RAL)--a precursor of retinoic acid (RA)--and glycolic acid (GA)--an AHA.


OBJECTIVE
To study the pharmacological properties of RALGA.


METHODS
The bioavailability of RAL into the skin after topical RALGA was studied by HPLC, and its bioconversion to RA was analysed by measuring the enzyme activity of retinaldehyde dehydrogenase and the RA content in the epidermis and dermis. The retinoid activity of RALGA was studied on the modulation of Hhb4 keratin mRNA on the tail of C57BL/6 mice, and its comedolytic properties on the size and density of dermal cysts and the morphology of sebaceous glands in hairless mice.


RESULTS
Epidermal and dermal concentrations of RAL and RA were higher after RALGA treatment, as compared to both RAL 0.1% alone and RA 0.05% alone; this indicates that the presence of GA favours the bioavailability and biotransformation of RAL into RA. The retinoid activity of RALGA (suppression of Hhb4 mRNA keratin) was similar to that of RAL alone, indicating that the presence of GA does not interfere with specific retinoid activity; GA alone had no effect in this test, which confirms the specificity of Hhb4 mRNA keratin modulation for retinoid activity. The diameter and the density of dermal cysts as well as the size of sebaceous glands were significantly decreased by RALGA.


CONCLUSIONS
These observations indicate that the addition of an AHA such as GA to a retinoid such as RAL results in a better bioavailability of the retinoid, thus a higher delivery of RA, which potentiates the biological activities of the retinoid. This combination allows a delivery of high amounts of RA in the skin while preventing the side-effects usually observed with high concentrations of topical RA.
Tran
Christian
C
Department of Dermatology, University Hospital, Geneva, Switzerland. christian.tran@hcuge.ch
Kasraee
Behrooz
B
Grand
Denise
D
Carraux
Pierre
P
Didierjean
Liliane
L
Sorg
Olivier
O
Saurat
Jean-Hilaire
JH
D000445:Aldehyde Oxidoreductases / Q000032:analysis; D000818:Animals; D001682:Biological Availability; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003560:Cysts / Q000188:drug therapy; D003879:Dermatologic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D020405:Dermis / Q000201:enzymology / Q000378:metabolism; D004338:Drug Combinations; D004817:Epidermis / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006016:Glycolates / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007633:Keratins / Q000187:drug effects; D007641:Keratolytic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012627:Sebaceous Glands / Q000187:drug effects; D014212:Tretinoin / Q000032:analysis
D003879:Dermatologic Agents; D004338:Drug Combinations; D006016:Glycolates; D007641:Keratolytic Agents; C501639:diacneal; C031149:glycolic acid; D014212:Tretinoin; D007633:Keratins; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde