A Study Of Dopamine Oxidative Self-polymerization And Its Modified Alginate Hydrogel For Drug Delivery Application

Dopamine?DA?is a typical catechol-containing monomer with multiple functions.It is prone to oxidative self-polymerization in the presence of an alkaline environment or an oxidizing agent to form polydopamine?PDA?.By controlling the reaction conditions,DA can be deposited as a PDA coating on a variety of materials or oxidized-self-assembled into PDA microspheres?PDA Ps?.Natural anionic polysaccharide hydrogels such as sodium alginate?ALG?are difficult to achieve high drug loading capacity,because the ability of gel network to adsorb drug is weak.Traditional ionic crosslinked hydrogels tend to swell rapidly in normal saline and resulting in drug burst.In this paper,the effects of initiator conditions on DA oxidation self-polymerization and its sphericity were studied systematically.The sodium alginate was modified by DA/PDA components to optimize the gelation and drug adsorption properties.The specific research content of this paper is mainly divided into the following two parts:1.Methods to control oxidation reaction of DA and prepare PDA nanoparticlesWe systematically compared the characteristics of dopamine oxidation reaction under the conditions of ammonia?basic?and sodium periodate?acidic?.The sodium periodate initiation system was studied in detail,and the effects of reaction medium,concentration of monomer and initiator,reaction time and other factors on the composition of oxidation products and their self-assembly process were studied.The chemical composition and morphology of the products were characterized by ultraviolet-visible spectrophotometer?UV-Vis?,fourier transform infrared spectroscopy?FT-IR?,scanning electron microscopy?SEM?,transmission electron microscopy?TEM?and nanometer laser particle size analyzer?DLS?.Based on this,a reasonable speculation on the mechanism of oxidation self-polymerization was carried out.Drug loading and in vitro release experiments showed that PDA Ps had good adsorption capacity for gatifloxacin?GFLX?and had a certain sustained release performance.In vitro cytotoxicity test showed that low concentration PDA Ps had good biocompatibility.In vitro cytotoxicity experiments showed that low concentrations of PDA Ps have good biological compatibility,which provides a certain reference for its application in biomedical related fields.2.Preparation and characterization of dopamine/polydopamine modified alginate gel and its release to GFLX in vitroIn this experiment,dopamine-modified alginate hydrogels were prepared by physical blending and chemical copolymerization:?1?PDA particle-embedded hydrogel?ALG-PDA?was prepared by pre-preparing uniformly dispersed PDA Ps and dispersing into sodium alginate solution through Ca²⁺cross-linking.?2?Ammonia aqueous solution?AS?or sodium periodate?SP?was used to initiate DA reaction in the ALG solution,and then two hydrogels incorporated DA/PDA components,ALG-DA-AS and ALG-DA-SP,were prepared respectively by further crosslinking through Ca²⁺.The chemical composition and microstructure of the incorporated DA/PDA component in the hydrogel were characterized by UV-Vis,SEM,nuclear magnetic resonance?¹H NMR?and FT-IR.The sol-gel transition time of ALG-DA-SP hydrogel was determined by rheology characterizations.In the drug-loading and in vitro release experiments using gatifloxacin?GFLX?as a model drug,the three modified hydrogels have higher drug loading capacity and slower release rate than the pristine ALG hydrogel.In vitro cytotoxicity tests showed that the three hydrogels of ALG,ALG-DA-AS and ALG-DA-SP had relatively low cytotoxicity.The swelling experiments showed that ALG-DA-SP hydrogel could maintain its complete structure after 72 hours immersion in normal saline due to its covalent cross-linking structure.In this experiment,the exact statuses of incorporated DA/PDA components in hydrogel matrix and their contributions to gel formation,structure and performance as drug carriers was systematically characterized.This provides a new strategy for the development of in situ hydrogels for medical and pharmaceutical applications.