Arnedo A, Espuelas S, Irache J M
Departamento de Farmacia y Tecnología Farmacéutica, Centro Galénico, Universidad de Navarra, 31008 Pamplona, Spain.
Int J Pharm. 2002 Sep 5;244(1-2):59-72. doi: 10.1016/s0378-5173(02)00300-9.
The goal of this study was the evaluation of albumin nanoparticles as drug delivery systems for antisense oligonucleotides. Bovine serum albumin (BSA) nanoparticles were prepared by a coacervation process. A phosphodiester oligonucleotide was either incorporated into the matrix of the particles by incubation with the albumin prior the coacervation process or adsorbed onto the pre-formed nanoparticles. Incorporated and/or adsorbed oligonucleotide was estimated by capillary electrophoresis and fluorescence spectroscopy. The adsorbed amount of oligonucleotide was dramatically dependent on the pH of the medium. Desorption of the oligonucleotide was also affected by the pH and ionic strength of the medium. This indicated that electrostatic forces play a major role in the interaction between the oligonucleotide and the nanoparticles. When the oligonucleotide was incubated with the albumin prior to nanoparticle formation, the profile of release confirmed that a fraction was incorporated into the matrix and its release was controlled by the albumin degradation. The hybridisation capability of the oligonucleotide in both nanoparticle formulations was retained. However, only the oligonucleotide incorporated into the nanoparticle matrix was protected against enzymatic degradation.
本研究的目的是评估白蛋白纳米颗粒作为反义寡核苷酸药物递送系统的性能。通过凝聚法制备牛血清白蛋白（BSA）纳米颗粒。在凝聚过程之前，通过与白蛋白孵育将磷酸二酯寡核苷酸掺入颗粒基质中，或者将其吸附到预先形成的纳米颗粒上。通过毛细管电泳和荧光光谱法估算掺入和/或吸附的寡核苷酸。寡核苷酸的吸附量极大地取决于介质的pH值。寡核苷酸的解吸也受介质的pH值和离子强度影响。这表明静电力在寡核苷酸与纳米颗粒之间的相互作用中起主要作用。当在纳米颗粒形成之前将寡核苷酸与白蛋白孵育时，释放曲线证实有一部分被掺入基质中，其释放受白蛋白降解的控制。两种纳米颗粒制剂中寡核苷酸的杂交能力均得以保留。然而，只有掺入纳米颗粒基质中的寡核苷酸受到酶降解的保护。
