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    Poly(amidoamine) Dendrimer as a Respiratory Nanocarrier: Insights from Experiments and Molecular Dynamics Simulations

    Year: 2019

    Journal: Langmuir, Volume 35, 1-Apr, page 5364–5371

    Authors: Tian, Fujia; Lin, Xubo; Valle, Russell P.; Zuo, Yi Y.; Gu, Ning

    Organizations: Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities; Startup Fund of Beijing Advanced Innovation Center for Biomedical Engineering; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [61420106012, 61601227]; NSFNational Science Foundation (NSF) [CBET-1254795, CBET-1604119]

    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 GS-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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