Dailey L A, Kleemann E, Wittmar M, Gessler T, Schmehl T, Roberts C, Seeger W, Kissel T
Department of Pharmaceutics and Biopharmacy, Philipps University, Ketzerbach 63, 35037 Marburg, Germany.
Pharm Res. 2003 Dec;20(12):2011-20. doi: 10.1023/b:pham.0000008051.94834.10.
This study describes the development of surfactant-free, biodegradable nanoparticle systems with varying physicochemical properties and their suitability for pulmonary application via nebulization.
Nanoparticle suspensions were formulated from the branched polyester, diethylaminopropyl amine-poly(vinyl alcohol)-grafted-poly(lactide-co-glycolide) (DEAPA-PVAL-g-PLGA) alone, as well as with increasing amounts of carboxymethyl cellulose (CMC). Particle size, zeta potential, turbidity, and morphology (atomic force microscopy) were characterized. Three formulations were chosen for further study: Cationic nanoparticles without CMC, cationic nanoparticles with CMC, and anionic nanoparticles with an excess of CMC. Nanoparticle degradation was characterized, as well as stability during nebulization. Nanoparticle-cell interactions were investigated and quantified using confocal laser scanning microscopy and fluorescence spectrometry.
Nanoparticles ranged in size from 70-250 nm and displayed zeta potentials of +58.9 to -46.6 mV. Anionic nanoparticles showed the highest stability during nebulization. The degradation rate of each nanoparticle formulation decreased with increasing amounts of CMC. Cell association was highest among cationic nanoparticles (57% and 30%, respectively), although these were not internalized. Despite a lower rate of cell association (3%), anionic nanoparticles were internalized by A549 cells.
Surfactant-free nanoparticles from DEAPA-PVAL-g-PLGA are versatile drug delivery systems; however, only the anionic formulations investigated were proven suitable for aerosol therapy.
本研究描述了具有不同物理化学性质的无表面活性剂、可生物降解的纳米颗粒系统的开发及其通过雾化用于肺部应用的适用性。
纳米颗粒悬浮液由支化聚酯二乙氨基丙基胺 - 聚乙烯醇接枝聚丙交酯 - 乙交酯共聚物（DEAPA - PVAL - g - PLGA）单独配制，以及与增加量的羧甲基纤维素（CMC）一起配制。对粒径、zeta电位、浊度和形态（原子力显微镜）进行了表征。选择三种制剂进行进一步研究：不含CMC的阳离子纳米颗粒、含CMC的阳离子纳米颗粒和含过量CMC的阴离子纳米颗粒。对纳米颗粒降解以及雾化过程中的稳定性进行了表征。使用共聚焦激光扫描显微镜和荧光光谱法研究并定量了纳米颗粒与细胞的相互作用。
纳米颗粒的尺寸范围为70 - 250 nm，zeta电位为 +58.9至 -46.6 mV。阴离子纳米颗粒在雾化过程中显示出最高的稳定性。每种纳米颗粒制剂的降解速率随着CMC量的增加而降低。阳离子纳米颗粒中的细胞结合率最高（分别为57%和30%），尽管它们没有被内化。尽管细胞结合率较低（3%），但阴离子纳米颗粒被A549细胞内化。
来自DEAPA - PVAL - g - PLGA的无表面活性剂纳米颗粒是通用的药物递送系统；然而，仅所研究的阴离子制剂被证明适用于气溶胶疗法。
