Influence of surface chemistry of poly(amidoamine) dendrimers on Caco-2 cell monolayers
Influence of surface chemistry of poly(amidoamine) dendrimers on Caco-2 cell monolayers
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DOI：
10.1177/0883911503018001002
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发表时间：
2003-01-01
影响因子：
1.7
通讯作者：
Ghandehari, H
中科院分区：
文献类型：
--
作者：
El-Sayed, M;Ginski, M;Ghandehari, H
本研究的目的是通过监测跨上皮电阻（TEER）、甘露醇渗透性和乳酸脱氢酶（LDH）泄漏，分别研究聚酰胺-胺、PAMAM、树枝状聚合物表面电荷对Caco-2细胞单层完整性、细胞旁渗透性和细胞活力的影响。中性PAMAM-OH，第2-4代（G2-G4）和阴离子PAMAM-COOH将（G-0.5-G4.5）树枝状聚合物与Caco-2细胞单层在供体浓度为0.1、1.0和10.0 mM下孵育90、150和210 min。G1.5和G4.5树枝状聚合物未引起TEER或甘露醇透过Caco-2细胞单层的任何显著变化。然而，阴离子G2.5和G3.5树枝状聚合物引起TEER值的孵育时间依赖性下降，甘露醇渗透性增加高达6倍。所有阴离子PAMAM-COOH树枝状聚合物引起孵育时间，浓度和代依赖性LDH泄漏，没有观察到与中性PAMAM-OH树枝状聚合物。这些研究表明阴离子树枝状聚合物可以增强跨Caco-2细胞单层的细胞旁转运的大小和/或电荷“窗口”，进一步证实了它们作为口服药物递送的药物载体和渗透促进剂的潜力。
The objective of this research was to investigate the effect of surface charge of poly(amidoamine), PAMAM, dendrimers on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers by monitoring the transepithelial electrical resistance (TEER), mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. Neutral PAMAM-OH, generations 2-4 (G2-G4), and anionic PAMAM-COOH (G-0.5-G4.5) dendrimers were incubated with Caco-2 cell monolayers at donor concentrations of 0.1, 1.0, and 10.0 mM for 90, 150, and 210 min. Neutral G2-G4 and anionic G-0.5, G0.5, G1.5 and G4.5 dendrimers did not cause any significant change in TEER or mannitol permeability across Caco-2 cell monolayers. Anionic G2.5 and G3.5 dendrimers, however, caused an incubation time-dependant decline in TEER values and up to a 6-fold increase in mannitol permeability. All anionic PAMAM-COOH dendrimers caused an incubation time-, concentration-, and generation-dependant LDH leakage that was not observed with neutral PAMAM-OH dendrimers. These studies suggest a size and/or charge "window" where anionic dendrimers may enhance paracellular transport across Caco-2 cell monolayers further confirming their potential as drug carriers and permeation enhancers for oral drug delivery.