School of Pharmacy, Yantai University, Yantai 264005, P. R. China.
Biol Pharm Bull. 2010;33(8):1371-7. doi: 10.1248/bpb.33.1371.
The aim of this study was to investigate the effect of Poly(amidoamine) (PAMAM) dendrimers on corneal permeation of puerarin (PUE). Permeation studies were performed using excised cornea of rabbits by a Valia-Chien diffusion apparatus. Drug-treatment studies were carried out by measuring the penetration of puerarin on cornea in PAMAM-PUE physical mixture or PAMAM-PUE complex, and cornea-treatment studies were carried out by measuring the penetration of puerarin on PAMAM dendrimer pretreated cornea in puerarin solution. The results showed that the permeability coefficient of puerarin in PAMAM-PUE physical mixture was enhanced by 2.48 (G3), 1.99 (G4) and 1.36 (G5) times on average, respectively compared to control. However, no significant permeability enhancement of puerarin in PAMAM-PUE complex was found compared to control. This may attribute to free drug concentration was lower in PAMAM-PUE complex which served as a depot and exhibited slow-released behavior of drug. Cornea-treatment studies showed that the lag time of puerarin was decreased, while the cumulative amount within 2.5 h (Q(2.5)) and the permeability coefficient of puerarin increased compared to control. The permeability coefficient of puerarin was linear correlated to the molecular weight of PAMAM dendrimer (r(2)=0.99). This indicates that higher generation of PAMAM dendrimer more easily interact with cornea or loosen the epithelium cell junctions than lower generation to increase the flux of puerarin. Overall, the study showed that PAMAM dendrimer increased the corneal permeation of puerarin mainly by altering the corneal barrier.
本研究旨在探讨聚酰胺-胺（PAMAM）树枝状聚合物对葛根素（PUE）角膜渗透的影响。采用离体兔角膜，通过 Valia-Chien 扩散装置进行渗透研究。通过测量 PAMAM-PUE 物理混合物或 PAMAM-PUE 复合物中葛根素的渗透，进行药物处理研究，通过测量葛根素预处理的 PAMAM 树枝状聚合物角膜上的葛根素渗透，进行角膜处理研究。结果表明，与对照相比，PAMAM-PUE 物理混合物中葛根素的渗透系数分别平均提高了 2.48（G3）、1.99（G4）和 1.36（G5）倍。然而，与对照相比，PAMAM-PUE 复合物中葛根素的渗透增强没有显著差异。这可能归因于 PAMAM-PUE 复合物中游离药物浓度较低，作为储库，表现出药物缓慢释放的行为。角膜处理研究表明，葛根素的滞后时间缩短，而 2.5 小时内的累积量（Q（2.5））和葛根素的渗透系数与对照相比增加。葛根素的渗透系数与 PAMAM 树枝状聚合物的分子量呈线性相关（r（2）=0.99）。这表明，与低代 PAMAM 树枝状聚合物相比，高代 PAMAM 树枝状聚合物更容易与角膜相互作用或松弛上皮细胞连接，从而增加葛根素的通量。总之，该研究表明，PAMAM 树枝状聚合物主要通过改变角膜屏障来增加葛根素的角膜渗透。
