Study On Self-assembly Mechanism Of Chitosan/Carboxymethyl Chitosan And Drug Release Performance

With the acceleration of industrialization and informatization,irregular living habits and deteriorating living environment lead to the increase in the number of cancer patients.Although a large number of active compounds can be used as therapeutic drugs,their bioavailability is too low to apply.Nano-drug carriers are widely used in biology and medicine,because they can target transport and controllable release of drugs while effectively avoiding the degradation of drug molecules.Chitosan（CS）,as the only natural alkaline polyelectrolyte polysaccharide,has great application potential in biological field because of its good biocompatibility and activity,biological adhesion and biodegradability.Since the poor solubility of high molecular weight chitosan,chitosan is usually degraded or modified to expand its application field.On the other hand,Carboxymethyl Chitosan（CMCS）,a derivative of chitosan,is often used as a drug carrier because of its low crystallinity,good water solubility and sensitive p H responsiveness.Based on the characteristics and advantages of natural polymers and polyelectrolyte,the CS/CMCS self-supporting nanoparticles with pH sensitivity were prepared by using chitosan and its derivative carboxymethyl chitosan as the drug carrier.And the structure,morphology and drug release properties of the nanoparticles were studied.The main contents and conclusions are shown as follows:（1）The lower molecular weight chitosan was obtained by oxidative degradation,ultrasonic degradation,irradiation degradation and ultrasonic synergistic oxidation degradation.The degradation condition was optimized and the molecular weight of the product was measured by the Ubbelohde viscometer.The optimal reaction conditions and product molecular weight of the four degradation modes are as follows:when the degradation conditions wasω_HCl=0.5%,V_H2O2=2.8 m L,T=55℃,t=8 h,the viscosity average molecular weight of oxidative degradation products was about 5.5×10³;when the degradation conditions wasω_HCl=0.7%,T=65℃,t=8 h,the viscosity average molecular weight of ultrasonic degradation was about 2.2×10⁵;when the dose of irradiation degradation was 250 kGy,the chitosan viscosity average molecular weight is about 1.1×10⁴ g/mol;when the degradation conditions wasω_HCl=0.3%,V_H2O2=2.8 m L,T=65℃,t=8 h,the viscosity average molecular weight of ultrasonic synergistic oxidation degradation products were about 1.6×10⁴g/mol.The influence of degradation method on structure was analyzed by infrared spectrum analysis.Compared with other methods of degradation,the irradiation degradation can be more simple and efficient,moreover,the structure of chitosan can be preserved after degradation.（2）CS/CMCS nanoparticles were prepared by emulsion-ion crosslinking method.The effect of reaction conditions on the particle size of microspheres was explored by the control variable method,and the best reaction conditions were M=18 million,m=0.01 g,t=50℃,t=90 min,2%TTP,at this time the particle size of microspheres was about 230 nm.The microstructure of CS/CMCS nanoparticles was observed by transmission electron microscope,and effects of the mass ratio between chitosan and carboxymethyl chitosan were discussed.The nanoparticles were in a regular spherical shape,and the sizes were approximately 220 nm,200 nm and 280nm,when m_cs:m_CMCS=1:1,1:1.4 and 1:2.2.With the increase mass of carboxymethyl chitosan,the micro-spherical double layer structure was more obvious.（3）The CS/CMCS/GST nanoparticles were prepared by diffusion adsorption and hydrogen bonding,and the release behavior of the drug-loading nanoparticles was studied.The molecular structure of drug-loading particle was determined by IR spectroscopy,and the encapsulation and drug-loading rate of nanoparticles were measured by ultraviolet spectrophotometer.Results show that CS/CMCS particles can successfully package the genistein.Under 37℃,the release dose of CS/CMCS drug-loading nanoparticles in the pH 6.8（cancer cells）was larger than that of pH7.4（normal fluid）.With the increase of CMCS mass ratio from 0,1.4 to 2.2,the encapsulation rate changed a little,but the p H responsiveness of CS/CMCS nanoparticles was increased with the increase of CMCS mass ratio,the cumulative release rate can increase from 70%to 86%and 90%.