反义寡核苷酸透过猪口腔黏膜的通透性

Permeability of antisense oligonucleotide through porcine buccal mucosa.

作者信息

Jasti B R, Zhou S, Mehta R C, Li X

机构信息

Department of Pharmaceutics and Medicinal Chemistry, School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA.

出版信息

Int J Pharm. 2000 Nov 4;208(1-2):35-9. doi: 10.1016/s0378-5173(00)00543-3.

DOI:10.1016/s0378-5173(00)00543-3

PMID:11064209

Abstract

Antisense oligonucleotides (AONs) that can modulate malfunctioning genes have a great potential to become future therapeutic agents. In this study, we investigated the feasibility of buccal delivery of AONs using ISIS 3082 as a model compound. An isocratic HPLC method was developed to quantify ISIS 3082. The permeability coefficient of this AON at 37 degrees C, determined by using side-by-side diffusion cells, was 1.05x10(-9) (cm/s). The flux of ISIS 3082 across buccal mucosa was dependent upon its concentration in the donor chamber. The permeation of ISIS 3082 was increased when 100 mM of sodium glycocholate was used as a permeation enhancer. The potential of delivering AONs via buccal route with the aid of permeation enhancers is explored in this study.

摘要

能够调节功能异常基因的反义寡核苷酸（AONs）具有成为未来治疗药物的巨大潜力。在本研究中，我们以ISIS 3082作为模型化合物，研究了经颊给药AONs的可行性。开发了一种等度高效液相色谱法来定量ISIS 3082。使用并列扩散池测定，该AON在37℃时的渗透系数为1.05×10⁻⁹（cm/s）。ISIS 3082穿过颊黏膜的通量取决于其在供体室中的浓度。当使用100 mM甘氨胆酸钠作为渗透促进剂时，ISIS 3082的渗透增加。本研究探讨了借助渗透促进剂经颊途径递送AONs的潜力。