Acetal-derivatized dextran: an acid-responsive biodegradable material for therapeutic applications.
Dextran, a biocompatible, water-soluble polysaccharide, was modified at its hydroxyls with acetal moieties such that it became insoluble in water but freely soluble in common organic solvents enabling its use in the facile preparation of acid-sensitive microparticles. These particles degrade in a pH-dependent manner: FITC-dextran was released with a half-life at 37 degrees C of 10 h at pH 5.0 compared to a half-life of approximately 15 days at pH 7.4. Both hydrophobic and hydrophilic cargoes were successfully loaded into these particles using single and double emulsion techniques, respectively. When used in a model vaccine application, particles loaded with the protein ovalbumin (OVA) increased the presentation of OVA-derived peptides to CD8+ T-cells 16-fold relative to OVA alone. Additionally, this dextran derivative was found to be nontoxic in preliminary in vitro cytotoxicity assays. Owing to its ease of preparation, processability, pH-sensitivity, and biocompatibility, this type of modified dextran should find use in numerous drug delivery applications.
Bachelder
Eric M
EM
Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Beaudette
Tristan T
TT
Broaders
Kyle E
KE
Dashe
Jesse
J
Fréchet
Jean M J
JM
D000080:Acetals / Q000737:chemistry; D000143:Acids / Q000737:chemistry; D000818:Animals; D017951:Antigen Presentation; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D001673:Biodegradation, Environmental; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D003911:Dextrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008422:Materials Testing; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D014612:Vaccines / Q000737:chemistry / Q000276:immunology
D000080:Acetals; D000143:Acids; D001672:Biocompatible Materials; D003911:Dextrans; D014612:Vaccines; C015219:fluorescein isothiocyanate dextran; D010047:Ovalbumin; D016650:Fluorescein-5-isothiocyanate