Poly(ethylene glycol)-polyethyleneimine NanoGel™ particles:: novel drug delivery systems for antisense oligonucleotides

被引：193

作者：

Vinogradov, S ^{[1
]}

Batrakova, E ^{[1
]}

Kabanov, A ^{[1
]}

机构：

[1] Univ Nebraska, Med Ctr 986025, Dept Pharmaceut Sci, Omaha, NE 68198 USA

来源：

COLLOIDS AND SURFACES B-BIOINTERFACES | 1999年 / 16卷 / 1-4期

基金：

美国国家科学基金会;

关键词：

hydrogel nanoparticles; poly(ethylene glycol); polyethyleneimine; drug delivery; antisense oligonucleotide; multidrug resistance;

D O I：

10.1016/S0927-7765(99)00080-6

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

A novel type of drug delivery system, termed NanoGel(TM) is proposed. NanoGel(TM) represent particles of a hydrophilic polymer network that were synthesized by cross-linking of polyethyleneimine (PEI) and carbonyldiimidazole-activated poly(ethylene glycol) (PEG) using emulsification;solvent evaporation technique. The resulting NanoGel(TM) was fractionated by gel-permeation chromatography. A major fraction with an average particle size of 120 plm was used in further experiments. Antisense phosphorothioate oligonucleotides (SODN) specific to human mdrl gene were incorporated in these NanoGel(TM) particles. Loading of NanoGel(TM) particles with SODN resulted in reduction of the particle effective diameter to 80 nm and decreased zeta-potential due to neutralization of the charge of PEI chains by SODN. Accumulation of SODN incorporated in NanoGel(TM) particles in multidrug resistant (MDR) human oral epidermoid carcinoma cells (KBv) was significantly increased compared to the free SODN. Furthermore, efficient transport of SODN-loaded NanoGel(TM) particles across polarized monolayers of human intestinal epithelial cells (Caco-2) was demonstrated. Finally, antisense SODNs incorporated in NanoGel(TM) particles were found to effectively inhibit expression of P-glycoprotein (P-gp) efflux pump in MDR cell lines. (C) 1999 Elsevier Science B.V. All rights reserved.

引用

页码：291 / 304

页数：14

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