Transepithelial transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers
Transepithelial transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers
复制标题
DOI：
10.1016/s0168-3659(02)00087-1
复制
发表时间：
2002-06-17
影响因子：
10.8
通讯作者：
Ghandehari, H
中科院分区：
文献类型：
--
作者：
El-Sayed, M;Ginski, M;Ghandehari, H
本研究的目的是研究聚酰胺胺(PAMAM)树枝状大分子的物理化学参数(如大小、分子质量、分子几何形状和表面胺基团的数量)对其通过Caco-2细胞单层的影响：研究了一系列0-4代PAMAM树枝状大分子(G0-G4)在根尖到基底(AB)和根尖(BA)方向上对Caco-2细胞单层的渗透性。通过测定跨皮细胞电阻(TEER)、甘露醇通透性和乳酸脱氢酶(LDH)漏出量，观察PAMAM树枝状大分子对Caco-2细胞单层的完整性、细胞旁通透性和活性的影响。G0、G1和G2表现出相似的AB透性，比高世代的AB透性中等高几倍。G0-G4的AB和BA渗透率随供体浓度和孵育时间的增加而增加。没有关于树枝状大分子对Caco-2细胞毒性的世代、浓度或孵化时间的渗透率值的报道。随着供体浓度、孵育时间和代次的增加，TEER值降低，甘露醇渗透性增加。G3和G4的LDH结果表明，Caco-2细胞的活力随着供体浓度、孵育时间和代数的增加而降低。G0-G2明显的渗透性，再加上它们对Caco-2细胞的无毒作用，表明它们作为水溶性聚合物药物载体在受控口服给药方面具有潜力。(C)2002 Elsevier Science B V保留所有权利。
The objective of this study was to investigate the influence of physiochemical parameters (such as size, molecular weight, molecular geometry, and number of surface amine groups) of poly (amidoamine) (PAMAM) dendrimers, on their permeability across Caco-2 cell monolayers: The permeability of a series of PAMAM dendrimers, generations 0-4 (G0-G4), was investigated across Caco-2 cell monolayers in both the apical to basolateral (AB) and basolateral to apical (BA) directions. The influence of PAMAM dendrimers on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers was also monitored by measuring the transepithelial electrical resistance (TEER), mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. G0, G1 and G2 demonstrated similar AB permeabilities, which were moderate several fold higher than the AB permeability of higher generations. The AB and BA permeability of G0-G4 typically increased with the increase in donor concentration and incubation time. Permeability values are not reported at generations, concentrations or incubation times that the dendrimers were toxic to Caco-2 cells. TEER values decreased and mannitol permeability increased as a function of donor concentration, incubation time, and generation number. LDH results for G3 and G4 indicate that Caco-2 cell viability was reduced with increasing donor concentration, incubation time, and generation number. The appreciable permeability of G0-G2, coupled with their nontoxic effects on Caco-2 cells, suggest their potential as water-soluble polymeric drug carriers for controlled oral drug delivery. (C) 2002 Elsevier Science B V All rights reserved.