Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin
Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin
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DOI：
10.1016/s0168-3659(03)00200-1
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发表时间：
2003-07-31
影响因子：
10.8
通讯作者：
Diwan, PV
中科院分区：
文献类型：
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作者：
Chauhan, AS;Sridevi, S;Diwan, PV
吲哚美辛，一种模型药物，具有不同浓度的三种类型的树枝状聚合物的水性制剂的经皮递送显示出随着每种树枝状聚合物的浓度增加，通量线性增加。这一结果与相溶解度研究相反，在相溶解度研究中观察到Higuchi的Δ曲线。药物的稳态通量显著增加，并且在0.2%w/v浓度的G4-NH2树枝状聚合物的情况下最高，与纯药物悬浮液相比，其显示出4.5的增强因子。在体内，在5小时内达到稳态通量，并且G4-NH2和G4-OH树枝状聚合物制剂的C-max值显著更高。G4-NH2（1.95倍）制剂的G4-OH的[AUC]（0 - 24 h）显著高于纯药物的[AUC]（0 - 24 h），但在G-4.5树枝状聚合物制剂的情况下仅略高。爪体积的%抑制显示出与药代动力学数据相当的趋势，并且与纯药物悬浮液相比，G4-NH 2和G4-OH制剂分别最大增加1.6倍和1.5倍。(C)2003 Elsevier B.V.保留所有权利。
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, 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) G4-OH of G4-NH2 (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. (C) 2003 Elsevier B.V. All rights reserved.