Preparation and Biophysical Characterization of Pluronic F127-Dendrimer Conjugate as a Delivery Agent of Antisense Oligonucleotides

Abstract

A series of pluronic F127 conjugated PAMAM dendrimer generation 5 were prepared to evaluate the potential use of dendrimer-pluronic conjugates as a delivery agent of antisense oligonucleotides. The structural features of the conjugates were identified by FT-IR and 1H-NMR spectra. The prepared dendrimer generation 5-pluronic F127 conjugates showed particle size in the range of 50 to 130 nm with reduced zeta potential. The electrophoretic property of conjugates was further confirmed by capillary zone electrophoresis (CZE), demonstrating the decrease in electrophoretic mobility of conjugates as the number of pluronic F127 on surface of dendrimer increases. The number of free amino groups on a pluronic F127 conjugated dendrimer was quantitatively determined by fluorescamine assay, measuring the fluorescence intensity of amino groups reactive to fluorescamine on dendrimer generation 5-pluronic F127 conjugates. In MTT assay, dendrimer G5-pluronic F127 conjugates were safe on gingival fibroblast cells and acute toxicity was reduced as the mole ratio of dendrimer to pluronic increased. Complex formation of dendrimer G5-pluronic F127 conjugates with oligonucleotides was dose dependent.