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  • Title: Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin.
    Author: Chauhan AS, Sridevi S, Chalasani KB, Jain AK, Jain SK, Jain NK, Diwan PV.
    Journal: J Control Release; 2003 Jul 31; 90(3):335-43. PubMed ID: 12880700.
    Abstract:
    The transdermal delivery of aqueous formulations of indomethacin, a model drug, with different concentrations of three types of dendrimer showed a linear increase in flux with increasing concentration of each of the dendrimers. This result was in contrast to phase solubility studies, where Higuchi's A(N) profile was observed. The steady-state flux of the drug increased significantly and was highest with the G4-NH2 dendrimer at 0.2% w/v concentration, which showed an enhancement factor of 4.5 compared to the pure drug suspension. In vivo, a steady-state flux was achieved in 5 h, and the C(max) values were significantly higher with G4-NH2 and G4-OH dendrimer formulations. The [AUC](0-24h) of G4-NH2 (2.27 times) and G4-OH (1.95 times) formulations were significantly higher than that of the pure drug, but was only marginally higher in the case of G-4.5 dendrimer formulation. The % inhibition of paw volume showed a trend comparable to the pharmacokinetic data and a maximum of 1.6- and 1.5-fold increase was found with G4-NH2 and G4-OH formulations, respectively, compared to the pure drug suspension.
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