Zobel H P, Werner D, Gilbert M, Noe C R, Stieneker F, Kreuter J, Zimmer A
Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
J Microencapsul. 1999 Jul-Aug;16(4):501-9. doi: 10.1080/026520499288942.
In the present study, oligonucleotides were adsorbed onto the surface of cationic liposomes and nanoparticles at different ratios. As a result, the surface charges of the colloidal carriers were decreased with increasing oligonucleotide concentration. At a certain oligonucleotide concentration, complete charge neutralization led to the aggregation of the carrier systems. Further increasing oligonucleotide concentrations reversed the surface charge of liposomes and nanoparticles to a negative one. Ultrasonication was investigated as a possible means for the homogenization of the formed aggregates. However, the use of ultrasonication led to a time-dependent damage of oligonucleotides adsorbed onto AH-Chol liposomes and MMAEMC-nanoparticles, as well as of unbound oligonucleotides. Nearly 60% of the oligonucleotides adsorbed to MMAEMC-nanoparticles and 65% of ODNs adsorbed to the liposomes were degraded by the effect of cavitation produced by ultrasonication within 10 min. In contrast, the oligonucleotides were protected from degradation when DEAE-stabilized PHCA-nanoparticles were employed as ODN carriers. More than 80% of the oligonucleotides entangled in the surface matrix of these nanoparticles remained intact.
在本研究中，寡核苷酸以不同比例吸附到阳离子脂质体和纳米颗粒表面。结果，随着寡核苷酸浓度的增加，胶体载体的表面电荷降低。在一定的寡核苷酸浓度下，完全电荷中和导致载体系统聚集。进一步增加寡核苷酸浓度会使脂质体和纳米颗粒的表面电荷反转成负电荷。研究了超声处理作为使形成的聚集体均匀化的一种可能方法。然而，使用超声处理会导致吸附在AH - Chol脂质体和MMAEMC - 纳米颗粒上的寡核苷酸以及未结合的寡核苷酸随时间受损。在10分钟内，超声空化作用使吸附到MMAEMC - 纳米颗粒上的寡核苷酸近60%以及吸附到脂质体上的寡核苷酸65%发生降解。相比之下，当使用DEAE稳定的PHCA - 纳米颗粒作为寡核苷酸载体时，寡核苷酸受到保护而不被降解。缠绕在这些纳米颗粒表面基质中的寡核苷酸超过80%保持完整。
