Zimmer A
Biocenter, Institute for Pharmaceutical Technology, University of Frankfurt, Frankfurt am Main, Germany.
Methods. 1999 Jul;18(3):286-95, 322. doi: 10.1006/meth.1999.0786.
Polyalkylcyanoacrylate nanoparticles are effective colloidal drug carriers and were prepared by an emulsion polymerization process. Antisense oligonucleotides were loaded on the particles by adsorption. A cationic polymer, DEAE-dextran, was incorporated into the particle matrix or a cationic hydrophobic detergent (CTAB) was used to form a lipophilic oligonucleotide ion pair. Enzymatic digestion of the oligonucleotides was almost quantitatively inhibited by this nanoparticle complex and cellular uptake by different cell lines was significantly enhanced. In vivo the biodistribution of the oligonucleotide nanoparticle complex resulted in targeting of oligonucleotides to the liver. Improvements in antisense treatments with nanoparticles were demonstrated for tumor therapy as well as for antiviral applications.
聚烷基氰基丙烯酸酯纳米颗粒是有效的胶体药物载体，通过乳液聚合工艺制备。反义寡核苷酸通过吸附作用负载在颗粒上。将阳离子聚合物二乙氨基乙基葡聚糖掺入颗粒基质中，或使用阳离子疏水去污剂（十六烷基三甲基溴化铵）形成亲脂性寡核苷酸离子对。这种纳米颗粒复合物几乎能定量抑制寡核苷酸的酶促消化，并且显著增强了不同细胞系对其的细胞摄取。在体内，寡核苷酸纳米颗粒复合物的生物分布导致寡核苷酸靶向肝脏。纳米颗粒在反义治疗中的改进在肿瘤治疗以及抗病毒应用中都得到了证实。
