title: Synthesis and characterization of acetalated dextran polymer and microparticles with ethanol as a degradation product.
abstract: In the field of drug delivery, pH-sensitive polymeric microparticles can be used to release therapeutic payloads slowly in extracellular conditions (pH 7.4) and faster in more acidic areas in vivo, such as sites of inflammation, tumors, or intracellular conditions. Our group currently uses and is further developing the pH-sensitive polymer acetalated dextran (Ac-DEX), which is a biodegradable polymer with highly tunable degradation kinetics. Ac-DEX has displayed enhanced delivery of vaccine and drug components to immune and other cells, making it an extremely desirable polymer for immune applications. Currently, one of the degradation products of Ac-DEX is methanol, which may cause toxicity issues if applied at high concentrations with repeated doses. Therefore, in this manuscript we report the first synthesis and characterization of an Ac-DEX analog which, instead of a methanol degradation product, has a much safer ethanol degradation product. We abbreviate this ethoxy acetal derivatized acetalated dextran polymer as Ace-DEX, with the 'e' to indicate an ethanol degradation product. Like Ac-DEX, Ace-DEX microparticles have tunable degradation rates at pH 5 (intracellular). These rates range from hours to several days and are controlled simply by reaction time. Ace-DEX microparticles also show minimal cytotoxicity compared to commonly used poly(lactic-co-glycolic acid) (PLGA) microparticles when incubated with macrophages. This study aims to enhance the biocompatibility of acetalated dextran-type polymers to allow their use in high volume clinical applications such as multiple dosing and tissue engineering.
authors: William G. Lowrie Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, Ohio 43210, United States.
authors: Kevin J
authors: KJ
authors: Kauffman
authors: Clement
authors: C
authors: Do
authors: Sadhana
authors: S
authors: Sharma
authors: Matthew D
authors: MD
authors: Gallovic
authors: Eric M
authors: EM
authors: Bachelder
authors: Kristy M
authors: KM
authors: Ainslie
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003911:Dextrans / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007107:Immune System; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008863:Microspheres; D008956:Models, Chemical; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014612:Vaccines / Q000737:chemistry
chemical_list: D003911:Dextrans; D011108:Polymers; D013778:Tetrazolium Salts; D013844:Thiazoles; D014612:Vaccines; D000431:Ethanol; C022616:thiazolyl blue