单层
树枝状大分子
纳米载体
二棕榈酰磷脂酰胆碱
肺表面活性物质
化学
分子动力学
生物物理学
药物输送
纳米技术
材料科学
有机化学
计算化学
膜
磷脂
磷脂酰胆碱
生物化学
生物
作者
Fujia Tian,Xubo Lin,Russell P. Valle,Yi Y. Zuo,Ning Gu
出处
期刊:Langmuir
[American Chemical Society]
日期:2019-03-19
卷期号:35 (15): 5364-5371
被引量:17
标识
DOI:10.1021/acs.langmuir.9b00434
摘要
Pulmonary drug delivery is superior to the systemic administration in treating lung diseases. An optimal respiratory nanocarrier should be able to efficiently and safely cross the pulmonary surfactant film, which serves as the first biological barrier for respiratory delivery and plays paramount roles in maintaining the proper mechanics of breathing. In this work, we focused on the interactions between poly(amidoamine) (PAMAM) dendrimers and a model pulmonary surfactant. With combined Langmuir monolayer experiments and coarse-grained molecular dynamics simulations, we studied the effect of environmental temperature, size, and surface property of PAMAM dendrimers (G3-OH, G3-NH2, G5-OH, and G5-NH2) on the dipalmitoylphosphatidylcholine (DPPC) monolayer. Our simulations indicated that the environmental temperature could significantly affect the influence of PAMAM dendrimers on the DPPC monolayer. Therefore, results obtained at room temperature cannot be directly applied to elucidate interactions at body temperature. Simulations at body temperature found that all tested PAMAM dendrimers can easily penetrate the lipid monolayer during the monolayer expansion process (mimicking “inhalation”), and the cationic PAMAM dendrimers (−NH2) show promising penetration ability during the monolayer compression process (mimicking “expiration”). Larger PAMAM dendrimers (G5) adsorbed onto the lipid monolayer tend to induce structural collapse and inhibit normal phase transitions of the lipid monolayer. These adverse effects could be mitigated in the subsequent expansion–compression cycle. These findings suggest that the PAMAM dendrimer may be used as a potential respiratory drug nanocarrier.
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