Open AccessNanoparticle System Based on Amino-Dextran as a Drug Delivery Vehicle: Immune-Stimulatory CpG-Oligonucleotide Loading and Delivery
Author(s) -
Hien Van Nguyen,
Katrin Campbell,
Gavin F. Painter,
Sarah L. Young,
Greg F. Walker
Publication year - 2020
Publication title -
pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.054
H-Index - 50
ISSN - 1999-4923
DOI - 10.3390/pharmaceutics12121150
Subject(s) - dextran , chemistry , zeta potential , conjugated system , oligonucleotide , biophysics , nanoparticle , biochemistry , materials science , nanotechnology , biology , organic chemistry , dna , polymer
The aim of this study is to prepare and characterize an amino-dextran nanoparticle (aDNP) platform and investigate two loading strategies for unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide. aDNP was prepared by desolvation of amino-dextran followed by the chemical crosslinking of amino groups. Size, surface charge, and surface morphology of aDNP was determined by dynamic light scattering and transmission electron microscopy. CpG was either loaded onto aDNP by adsorption (CpG-adsorbed-aDNP) or conjugated to aDNP (CpG-conjugated-aDNP). In vitro cytokine production by bone marrow-derived dendritic cells (BMDCs) was measured by flow cytometry. aDNPs size and zeta potential could be controlled to produce uniform particles in the size range of 50 to 300 nm, surface charge of -16.5 to +14 mV, and were spherical in shape. Formulation control parameters investigated included the anti-solvent, water-to-anti-solvent ratio, level of amine functionality of dextran, and the molar ratio of glutaraldehyde to amine. aDNP could be lyophilized without additional cryoprotectant. Unloaded cationic aDNP (+13 mV) showed acceptable in vitro hemolysis. Unloaded and CpG-loaded aDNPs showed no cytotoxicity on BMDCs. CpG-loaded nanoparticles stimulated cytokine production by BMDCs, the level of cytokine production was higher for CpG-conjugated-aDNP compared to CpG-absorbed-aDNP. aDNP is a promising new drug delivery platform as its offers versatility in loading and tuning of particle properties.