Fabrication Of Multi-responsive Polymeric Nanocapsules And Nanocomposite Hybrid Hyaluronic Acid Hydrogel And The Application In Drug Controlled Release

During the past decade, the rapid development of biomedical and tissueengineering, polymeric nanoparticles and biodegradable cross-linking polymers,suchas hydrogels et al, have attracted much attention due to their wide applications inbiomedical fields, especially for the delivery and controlled release of life-activecompounds both in vitro and in vivo. However, controlling the kinetics of releasefrom such polymer-based drug delivery systems remains challenging, and the lowdrug loading capacity, poor biodegradability severely limit their use in many practicalapplications. In this dissertation, we designed a pH/temperature dual responsivepolymeric nanocapsules and biodegradable hyaluronic acid nanocomposite hydrogel,a dual drug delivery systems, and study on the drug controlled release properties.In the first part of this paper，the hairy poly(methacrylic acid-co-divinylbenzene)-g-poly(N-isopropylacrylamide)(P(MAA-co-DVB)-g-PNIPAm) nanocapsules withpH-responsive P(MAA-co-DVB) inner shell and temperature-responsive PNIPAmbrushes were prepared by combined distillation-precipitation copolymerization andsurface thiol-ene click grafting reaction using3-(trimethoxysilyl)propylmethacrylate-modified silica (SiO2-MPS) nanospheres as a sacrificial core material.The well-defined PNIPAm was synthesized by a reversible addition fragmentationchain transfer (RAFT) polymerization and reduced to generate a thiol group at thechain end, and then was integrated into the nanocapsules via thiol-ene click reaction.The surface thiol-ene click reaction conduced to high grafting density of PNIPAmbrushes which decreased from0.70chains/nm2to0.15chains/nm2with increasing themolecular weight of grafted PNIPAm chains. Using a water soluble doxorubicinhydrochloride (DOX·HCl) as a model molecular, the tunable shell permeability of thenanocapsule was investigated in detail. The permeability constant can be tuned bycontrolling the thickness of the of P(MAA-co-DVB) inner shell, the grafting densityof the PNIPAm brushes, and changing the environmental pH and temperature. Thetunable shell permeability of the nanocapsule made the loaded guest moleculesrelease with manipulable releasing kinetics. In the second part of this paper，a degradable nanocomposite hydrogel withbiodegradable natural macromolecular HA as gel precursor was fabricated withhollow polymeric nanocapsules dispersed throughout the matrix, which particularlyincludes research on the drug loading and drug release behaviors. The systems wereresearched for the effects of the mass fraction of gel precursor, the concentration ofHRP and H2O2on the gelation time and the swelling behavior. The results ofexperiments show that within a certain range the gelation time is inverselyproportional to the mass fraction of gel precursor, the concentration of HRP and H2O2.With the increase of the mass fraction of the gel precursor, the swelling ratio of thesystem is improved. In vitro drug loading and release studies show that thenanocomposite hydrogel system can be used as a dual drug delivery system, and canbe carried out without damage to protein embedded. Furthermore, the sustained drugrelease of the nanocomposite hydrogel system is significantly better than theperformance of hollow polymer nanocapsules.