Sonochemical Preparation Of Multifunctional Drug-loaded Alanine Microorganogel And Its Targeting/controlled Release Performance

As a novel nano-or micro-scale polymer drug carrier,micro-organogel has attracted much attention in biology,medicine and related fields in recent years.It is not only because micro-organogel has good biocompatibility,usability,degradability and high loading capacity for drugs,but also because compared to other drug carrier materials,micro-organogel exhibits a three-dimensional network structure that has the function of swelling and contracting,which is very beneficial for the controlled release of drugs.In addition,the shells or surfaces of many micro-organogel often retain a large number of reactive groups,which provides great possibilities for further modification or functionalization of micro-organogel.Based on the synthesis of thermo-sensitive alanine gelling agent,the micro-organogel with both thermo-sensitive and redox-sensitive has been prepared by sonochemical method,and a multifunctional drug carrier has been designed and constructed by introducing functional particles.At the same time,this thesis also has systematically studied the morphology,particle size distribution and properties of multifunctional drug carriers.The main research contents are as follows:1.An amino acid-based organic gelling agent with a low molecular weight,namely N-lauroyl-l-alanine methyl ester?LAM?,has been synthesized by nucleophilic substitution reaction of lauroyl chloride and esterified 1-alanine.Then,by using LAM as a gelator and various vegetable oil as a dispersing agent,the thermo-sensitive organogel has been prepared.The intrinsic relationship between the phase transition temperature of the organogel and the concentration of LAM has been explored,and the an organogel with a 37 ?phase transition has been screened.2.By using the sonochemical method,the organogel and bovine serum albumin at the oil/water interface has been assembled to prepare a micro-organogel with thermo-sensitive and redox-sensitive abilities.The preparation of the micro-organogel and encapsulation of hydrophobic drugs can be completed at the same time.Then we have discussed the characterization and measurement of morphology,structure,particle size distribution,drug loading capacity and dispersibility of micro-organogel in water,and also have discussed the affecting factors of the particle size of micro-organogel,such as ultrasonic time,ultrasonic power,protein concentration,volume ratio of organogel phase to aqueous phase?O/W?,etc.,finally achieving the optimization of experimental conditions for preparing micro-organogel with small particle size and uniform dispersion.In addition,by studying the release behavior of the sample under different stimuli?temperature and reducing agent?,it has been proved that the controlled release ability of the drug-loaded micro-organogel is highly dependent on temperature and reducing agent.3.Based on the sonochemical preparation of drug-loaded micro-organogel,the graphene oxide quantum dots?GQDs?are modified on to the shell layer of the micro-organogel,and the magnetic ferroferric oxide nanoparticles?Fe₃O₄MNPs?have been loaded into the oil core,finally constructing a multifunctional drug carrier with targeting and fluorescence imaging properties.It has been found by fluorescence spectroscopy that the micro-organogel has good fluorescence properties after the successful combination with GQDs.The micro-organogel loaded with Fe₃O₄ MNPs still shows a high magnetic saturation intensity and retained the superparamagnetism of Fe₃O₄ MNPs.The magnetic separation experiments show that the micro-organogel has the best magnetic responsiveness when the content of Fe₃O₄ MNPs is higher than 10.0 mg/m L.Meanwhile,the drug release experiments show that the introduction of GQDs and Fe₃O₄ MNPs is not affecting the thermo-sensitive and redox-sensitive of micro-organogel release behavior.Therefore,with the help of the magnetic responsiveness of Fe₃O₄ MNPs and the fluorescent properties of GQDs,the targeted delivery of drug-loaded micro-organogel can be achieved as well as its drug tracer and bioimaging.