In vitro percutaneous absorption of genistein from topical gels through human skin.
The objective of this study was to formulate genistein as a topical gel with various penetration enhancers for increased permeation and retention in human skin. The high performance liquid chromatography assay method was validated for precision and reproducibility. The intra-day and inter-day precision as represented by the coefficient of variation (CV) of the peak areas were <0.44% and <0.67%, respectively. Further, the reproducibility was demonstrated by the CV of the assay at different genistein concentrations, which were <1.64%. Genistein was subjected to various stress conditions to obtain basic information on the appropriate pH and aqueous vehicle for formulating topical gels. Genistein was highly stable under neutral and oxidative conditions, but degraded to highly polar and nonpolar compounds under basic and acidic conditions, respectively. Menthol produced a 9- and 22-fold increase in the flux and skin retention of genistein, respectively, after 24 h of gel application as compared with the control (no enhancer). Cineole showed an approximately 7-fold increase in flux, but skin retention did not increase significantly. Transcutol increased the flux and skin retention of genistein by 5- and 7-fold, respectively. When Transcutol was formulated with Lauroglycol, there was a 13- and 9-fold increase in the flux and skin retention, respectively. Incorporation of penetration enhancers into the topical gel increased the skin permeation of genistein, so that the target delivery rate for its therapeutic effects can be achievable based on the in vitro human skin data generated in this study.
Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36830, USA.
Gurkishan
G
Chadha
Sateeshkumar
S
Sathigari
Daniel L
DL
Parsons
R
R
Jayachandra Babu
D000287:Administration, Topical; D000438:Alcohols / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D019833:Genistein / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008747:Methylcellulose / Q000737:chemistry; D010539:Permeability; D012153:Retention, Psychology; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013729:Terpenes / Q000737:chemistry
D000438:Alcohols; D005782:Gels; D013729:Terpenes; D008747:Methylcellulose; D019833:Genistein