Vlassov V V, Karamyshev V N, Yakubov L A
Institute of Bioorganic Chemistry, Siberian Division of the Russian Academy of Sciences, Novosibirsk.
FEBS Lett. 1993 Aug 2;327(3):271-4. doi: 10.1016/0014-5793(93)81002-h.
Benzylamide 5'-32P-oligonucleotide derivatives were shown to penetrate into mice organism when administered by various routes; intranasally, per os, intravaginally and per rectum. In all cases, the compounds are rapidly accumulated in blood and guts. Analysis of the radioactive material from blood and pancreas revealed intact oligonucleotides. Although concentrations of oligonucleotides in tissues differ considerably by the various methods of administration, the efficiency of delivery is sufficient to consider all the routes as being of therapeutic value. Dose effect on the efficiency of oligonucleotide penetration into mice suggests the transport to be a saturable process. Application of an oligonucleotide lotion on mice ear helices results in reproducible accumulation of radioactivity in the animal tissues. Effectiveness of oligonucleotide delivery into mouse through skin can be improved by using electrophoretic procedure.
苄基酰胺5'-32P-寡核苷酸衍生物经不同途径给药时，可穿透小鼠机体；途径包括鼻内给药、口服、阴道内给药和直肠给药。在所有情况下，这些化合物都会迅速在血液和肠道中蓄积。对血液和胰腺中的放射性物质进行分析，发现了完整的寡核苷酸。尽管通过不同给药方法，组织中寡核苷酸的浓度差异很大，但给药效率足以使所有途径都具有治疗价值。剂量对寡核苷酸穿透小鼠效率的影响表明，这种转运是一个可饱和的过程。在小鼠耳螺旋上涂抹寡核苷酸洗剂，可使放射性物质在动物组织中重现性蓄积。通过电泳程序，可提高寡核苷酸经皮肤给药进入小鼠体内的有效性。
