Preparation Of Nanocrystalline Cellulose And Drug Release Properties Based On Furfural Residue

The traditional drug treatment therapy has a series of problems such as short drug action time,high fluctuation of drug concentration and high risk of side effects.Slow-and controlled-release drug delivery systems have become the fastest growing new drug delivery system today.It has great potential for development in various drug delivery routes.Among them,drug carrier should have the characteristics of good biocompatibility,non-toxicity,good physical and mechanical properties.Nanocrystalline cellulose（NCC）is a high-strength nanocellulose with low cytotoxicity,biodegradability,good thermal stability and abundant surface hydroxyl groups.Because of its excellent performance,NCC has become one of the best choices of the preparation of drug carriers.In this study,biomass wastes furfural residue（FR）was used as the raw material.Furfural residue cellulose was prepared by formic acid separation.NCC was prepared by acid hydrolysis.NCC/chitosan microspheres were prepared by reversed-phase suspension polymerization.Finally,NCC/chitosan@β-cyclodextrin microspheres were obtained by grafting succinic acid andβ-cyclodextrin onto NCC/chitosan microspheres.The in vitro drug release performance of NCC/chitosan@β-cyclodextrin microspheres were evaluated using 5-fluorouracil as a model drug.The main research of this study are as follows:Firstly,NCC was prepared from furfural residue.Lignin was removed by dissolving the raw material in formic acid,and furfural residue cellulose was obtained through alkaline hydrogen peroxide bleaching.NCC was prepared by hydrolyzing furfural residue cellulose with a mixture of sulfuric acid（SA）,lactic acid（LA）,and water under ultrasonic assistance.The optimal preparation conditions were obtained by single-factor and orthogonal experiments.The reaction conditions were 30%sulfuric acid mass ratio,50%lactic acid mass ratio,reaction time 2.5 hours,reaction temperature 40 degrees.The yield was 68.88%.NCC was characterized by thermogravimetric analyzer,infrared spectroscopy,transmission electron microscopy,X-ray diffraction instrumentation.NCC was in the form of short rods with diameters of5-10 nm and lengths of 60-150 nm,with a crystallinity of 82.74%.Its initial decomposition temperature of 225.4℃ was higher than that of NCC prepared with sulfuric acid alone,which had a crystallinity of 80.46%and an initial decomposition temperature of 221.2℃.Secondly,NCC/chitosan microspheres were prepared.The optimal preparation conditions for the microspheres were determined through single-factor and orthogonal experiments,with chitosan dosage of 0.2 g,NCC dosage of 0.08 g,reaction time of 2h,Span-80 dosage of 0.02 g·mL^-1,speed of 600 rpm,temperature of 30℃,crosslinking agent dosage of 0.5 g,and oil-water ratio of 4:1.The microspheres were characterized using X-ray diffraction,infrared spectroscopy,scanning electron microscopy,and laser particle size measurement.The prepared microspheres showed uniform morphology and smooth surface,with an average particle size of 18.25μm and uniform particle size distribution of 0.348.The crystal structure of NCC and chitosan within the microspheres did not change.Thirdly,NCC/chitosan@β-cyclodextrin microspheres were produced.The optimal preparation conditions were obtained through single-factor experiments and response surface design experiments.NCC/chitosan microspheres were 0.1 g,cyclodextrin was0.061 g,and succinic acid was 0.174 g at 150℃.The maximum loading capacity of the prepared microspheres to 5-fluorouracil was 183.45 mg·g^-1.Infrared spectroscopy,laser particle size measurement,scanning electron microscopy,and X-ray diffraction characterization showed that theβ-cyclodextrin was successfully grafted and the microspheres had a smooth surface but a slightly altered shape,which was not as rounded as the NCC/chitosan microspheres.The average particle size was 22.35μm with a uniformity of 0.368.Finally,the drug release performance of NCC/chitosan@β-cyclodextrin microspheres were investigated.The performance of NCC/chitosan@β-cyclodextrin microspheres in releasing 5-fluorouracil were evaluated under different pH environments.The results showed that the drug-loaded microspheres had higher release rate and cumulative release under pH=1.5.The in vitro drug release profile was consistent with the primary kinetic model and Hill’s model.It showed that the microspheres were pH-sensitive and could be released under acidic conditions for 600min,providing a possibility for gastric drug delivery.