PH-responsive Drug Delivery Nanogel Particles Based On Chitosan

Chitosan is a well-known abundant and low-cost natural polymer. Due to itsbiocompatibility, bioadhesive, biodegradability, anti-bacterial and anti-tumor immuneenhancement and other physical and chemical properties, it has been widely used inthe field of drug delivery. Nevertheless, the high crystallinity and poor solubilitylargely limit its scope of application. Introduction of hydrophilic groups to chitosan bychemical modification is an effective way to improve the solubility and enhance theirphysical and chemical properties. There are reactive amino groups on the chitosanmolecular chain, with the introduction of the carboxyl by anhydride acylation,hydrogen destroying and solubility improving, thus it can apply for the preparation ofpH-responsive nanoparticles for drug release. Nanoparticles have many uniquephysical and chemical properties, such as quantum size effect, macroscopic quantumtunneling effect, surface effect, small size effect. Gel is polymer networkscross-linked by chemical bond, hydrogen bond, van der Waals or physicalentanglement formation; the volume will change when subjected to external stimuli,with swelling shrinkage properties. Nanoparticles after gelation will have bothproperties, thus it has broad application prospects in the field of drug release.In this paper, the water-soluble maleoyl chitosan (MCS) and succinyl Chitosan(SCS) were prepared respectively by using water as a medium and sodium carbonateas catalyst. Elemental analysis, FT-IR, XRD, TG were used to characterize thestructure of the products. It proved that succinic anhydride and maleic anhydridegrafted to chitosan successfully, and the acylation occurs at the amino groupsubstantially. To some extent, acylation of chitosan undermined the regularity of themolecular chain and reduced the original crystallinity significantly, increasing thewater-solubility greatly. When the molar ratio of maleic anhydride and chitosan was1.2and the molar ratio of sodium carbonate and maleic anhydride was0.6, the degreeof acylation of maleic anhydride was greater than others. When the molar ratio of succinic anhydride and chitosan was2.0and the molar ratio of sodium carbonate andsuccinic anhydride was0.8, the degree of acylation of succinic anhydride was greaterthan others. The particle size and Zeta potential under different pH values were testedby using Nano-ZS90Malvern Instruments, we found that both maleoyl chitosan andsuccinyl chitosan have a function of pH changes in the characteristics and have anisoelectric point, the former pH=3.01, the latter pH=3.54, indicating that both havepotential as a pH-responsive drug delivery.Chitosan-based nanogel particles were prepared by using two water-solubleacylated chitosan as raw materials with ion gel and self-assembly method. With theion-gel method, the corresponding acylated chitosan sodium was selected as ioncross-linking agent. The effect of concentration of reactants and the pH values ofreaction system on the formation of nano-particles was researched. SEM was used tocharacterize the structure of nanopaoticles. SEM images show that nano-gel particlesare trend to a ball, but most of them appear reunion, and it can not be diluted or plusthe release agent to spread out the nanoparticles. So it is not very good to prepare thechitosan-based nanogel particles by using the ion-gel method. With the self-assemblymethod, a high degree of acylated-chitosan was directly dissolved in the water, afterthat instillate the glacial acetic acid, formic acid, lactic acid solution directly, thenacylated-chitosan nanoparticles self-assemble to form gel particles. SEM imagesdisplay that nanaoparticles are spherical particles with no agglomeration, some ofthem secondary self-assemble to form a regular hexagon structure, some secondaryaggregates to form a straight line, which provides space and possibility for drugloading of some special structure moleculars. DLS tests show that the size ofnanoparticles swell by tens of nanometers to hundreds of nanometers after alkali,which both the size increased and display the pH-responsive. It can used to preparethe pH-responsive intelligent drug delivery system. Nanoscale gel particles powder ofacylated chitosan got by grinding, DLS tests show the size of nanoparticles is tens orhundreds of nanometers at the solution of pH=2.0, but increased to micron particlesize due to their swelling in buffer solution of pH=7.4, displaying a pH-responsive,which laid the foundation for subsequent drug loading that release in the smallintestine but not release in the gastric juices.