Kleemann E, Dailey L A, Abdelhady H G, Gessler T, Schmehl T, Roberts C J, Davies M C, Seeger W, Kissel T
Department of Pharmaceutics and Biopharmacy, Philipps-University, Ketzerbach 63, D-35037 Marburg, Germany.
J Control Release. 2004 Dec 10;100(3):437-50. doi: 10.1016/j.jconrel.2004.09.005.
Polyelectrolyte complexes between DNA and polyethylenimine (PEI) are promising non-viral delivery systems for pulmonary inhalation gene therapy and thus require sufficient stability during nebulization. The structure and stability of four different PEI-DNA polyplexes, namely branched (bPEI), linear (linPEI), poly(ethylene glycol)-grafted PEI (PEGPEI), biodegradable (bioPEI) PEI with DNA, were investigated. Using atomic force microscopy, the morphology of DNA and polyplexes before and after both air-jet and ultrasonic nebulization was characterized. The influence of nebulization on physico-chemical properties, particle size and zeta potential, was studied. Efficient DNA condensation to spherical particles was achieved with bPEI (90 nm) and PEGPEI (110 nm). By contrast, incomplete DNA condensations, seen as flower structures, were observed with linPEI (110 nm) and bioPEI (105 nm). Air-jet nebulization altered the polyplex structure to a greater extent than ultrasonic nebulization and resulted mainly in smaller and non-spherical particles (30-200 nm). Ultrasonic nebulization did not change the spherical structure or particle size of the polyplexes. In particular, the shape and size of the PEGPEI polyplexes did not change. We conclude that ultrasonic nebulization is a milder aerosolization method for gene delivery systems based on PEI. Additionally, PEGPEI-DNA polyplexes seem to be more stable than their counterparts, which may be advantageous in pulmonary inhalation gene therapy.
DNA与聚乙烯亚胺（PEI）之间的聚电解质复合物是用于肺部吸入基因治疗的有前景的非病毒递送系统，因此在雾化过程中需要足够的稳定性。研究了四种不同的PEI-DNA多聚体的结构和稳定性，即支化（bPEI）、线性（linPEI）、聚乙二醇接枝的PEI（PEGPEI）、可生物降解的（bioPEI）PEI与DNA形成的多聚体。使用原子力显微镜，对喷气雾化和超声雾化前后DNA和多聚体的形态进行了表征。研究了雾化对物理化学性质、粒径和zeta电位的影响。bPEI（90 nm）和PEGPEI（110 nm）可实现高效的DNA凝聚成球形颗粒。相比之下，观察到linPEI（110 nm）和bioPEI（105 nm）存在不完全的DNA凝聚，呈现为花状结构。喷气雾化比超声雾化对多聚体结构的改变更大，主要导致形成更小的非球形颗粒（30 - 200 nm）。超声雾化未改变多聚体的球形结构或粒径。特别是，PEGPEI多聚体的形状和大小没有变化。我们得出结论，超声雾化对于基于PEI的基因递送系统是一种更温和的雾化方法。此外，PEGPEI-DNA多聚体似乎比其他多聚体更稳定，这在肺部吸入基因治疗中可能具有优势。
