Caproyl-Modified G2 PAMAM Dendrimer (G2-AC) Nanocomplexes Increases the Pulmonary Absorption of Insulin
Caproyl-Modified G2 PAMAM Dendrimer (G2-AC) Nanocomplexes Increases the Pulmonary Absorption of Insulin
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己酰基修饰的 G2 PAMAM 树枝状聚合物 (G2-AC) 纳米复合物可增加胰岛素的肺部吸收
DOI：
10.1208/s12249-019-1505-x
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发表时间：
2019-08
影响因子：
3.3
通讯作者：
Yueyi Deng
中科院分区：
文献类型：
--
作者：
Chengyun Yan;Jiwei Gu;Yuguang Lv;Weiguo Shi;Yuefeng Wang;Ying Liao;Yueyi Deng
本实验旨在通过肺部途径研究己烷修饰的G2 PAMAM树状大分子（G2- ac）对多肽和蛋白类药物的吸收增强作用（AEE）。本研究合成了己酸修饰的G2 PAMAM树状大分子偶联物，并对有无G2- ac的胰岛素肺吸收模型进行了评价。结果表明，G2-AC6在不同的G2-AC羧化水平下对胰岛素表现出最大的AEE。G2-AC6能显著促进胰岛素的吸收，且其AEE呈浓度依赖性。在毒性试验中，G2-AC6在0.1% （w/v）至1.0% （w/v）的浓度范围内对肺膜没有可测量的细胞毒性。结果表明，G2-AC6显著降低CF的TEER值，提高CF的Papp值。结果表明，G2-AC6可通过细胞旁通路和细胞外通路的结合穿越上皮细胞。这些结果表明，较低浓度（低于1.0%,w/v）的G2-AC6可能是有希望的吸收促进剂，可以增加多肽和蛋白质药物的肺部吸收。
We aimed to investigate the absorption-enhancing effect (AEE) of caproyl-modified G2 PAMAM dendrimer (G2-AC) on peptide and protein drugs via the pulmonary route. In this study, G2 PAMAM dendrimer conjugates modified with caproic acid was synthesized, the pulmonary absorption of insulin as models with or without G2-AC were evaluated. The results indicated that G2-AC6 exhibited a greatest AEE for insulin in various caproylation levels of G2-AC. G2-AC6 could significantly enhance the absorption of insulin, and the AEE of G2-AC6 was concentration-dependent. In toxicity tests, G2-AC6 displayed no measurable cytotoxicity to the pulmonary membranes over a concentration range from 0.1% (w/v) to 1.0% (w/v). Measurements of the TEER and permeability showed that G2-AC6 significantly reduced the TEER value of CF and increased its Papp value. The results suggested that G2-AC6 could cross epithelial cells by means of a combination of paracellular and transcellular pathways. These findings suggested G2-AC6 at lower concentrations (below 1.0%, w/v) might be promising absorption enhancers for increasing the pulmonary absorption of peptide and protein drugs.
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DOI：
--
发表时间：
1996
期刊：
Yao xue xue bao = Acta pharmaceutica Sinica
影响因子：
--
作者：
D. Abdullah;Ping Qn;Liu Gj
通讯作者：
D. Abdullah;Ping Qn;Liu Gj
影响因子：
3.8
作者：
Bai, Shuhua;Thomas, Chandan;Ahsan, Fakhrul
通讯作者：
Ahsan, Fakhrul
影响因子：
3.5
作者：
HO, W;FURST, A
通讯作者：
FURST, A
影响因子：
3.7
作者：
S. Okumura;Y. Fukuda;Kanae Takahashi;T. Fujita;A. Yamamoto;S. Muranishi
通讯作者：
S. Okumura;Y. Fukuda;Kanae Takahashi;T. Fujita;A. Yamamoto;S. Muranishi
影响因子：
5.6
作者：
Paranjpe M;Müller-Goymann CC
通讯作者：
Müller-Goymann CC