Construction And Drug Sustained Release Of Stimulus Response Cellulose Based Aerogel

The anticancer drug 5-fluorouracil has a short half-life,and infusion therapy is often used to treat diseases.The development of adjustable drug release time and portable drug carriers is very beneficial to the efficient use of drugs.Most of the existing drug carriers are artificially synthesized,which has poor biocompatibility,non-biodegradability,complicated preparation,and relatively large side effects.Cellulose aerogel has an excellent three-dimensional network structure,good biocompatibility and easy biodegradability,which is a good carrier for loading drugs.However,the currently cellulose aerogel has poor structural feasibility,low drug loading,and short drug release time,which severely limits its application value in drug delivery.The low drug loading and short release time of cellulose aerogel are due to the fact that there the larger pore size and fewer surface functional groups in cellulose aerogels,and it cannot efficiently form hydrogen bonds,van der Waals forces and electrostatic attraction during the process of combining with the drug 5-fluorouracil.In response to the above problems,this research was based on hydroxypropyl methylcellulose and carboxymethyl cellulose,using free radical copolymerization,carbon nanotubes and graphene oxide doping,etc.,to build series of stimulus-responsive cellulose-based aerogel drug carriers with temperature sensitivity,temperature and pH dual response,etc.The effect of active sites on drug loading during drug loading was studied;the network structure and drug loading performance of aerogels were adjusted.The amount and rate of drug release under different environments had been studied,revealing the mechanism of the active site’s influence on drug loading and sustained release performance.The details were as follows:(1)By introducing temperature-sensitive monomers with amino active sites,to prepare temperature-sensitive cellulose-based aerogels,adjust the network structure and drug-loading properties of aerogels,and study the effects of amino active sites on drug loading and sustained release performance.Using hydroxypropyl methyl cellulose(HPMC)as raw material,N-isopropyl acrylamide(NIPAM)as temperature-sensitive monomer,to prepare a semi-interpenetrating network HPMC-NIPAM temperature-sensitive aerogel through free radical polymerization.Through FTIR、XRD、XPS、elemental analysis、TGA、SEM and other modern techniques to analyze the microstructure and drug loading performance of temperature sensitive HPMC-NIPAM aerogel.The results showed that the introduction of NIPAM monomer was beneficial to enhance the cross-linking of cellulose molecules and realize the efficient construction of aerogel structure.The formed HPMC-NIPAM temperature-sensitive cellulose aerogel had higher porosity and lower density and good thermal stability.With the increase of the amount of NIPAM added,the density of HPMC-NIPAM temperature-sensitive cellulose aerogel increased,and the drug loading increased from 152.7 mg/g to 157.5 mg/g.Under the same release time of 300 min,the drug release rate at 37℃was significantly faster than that at 25℃,which had good temperature response performance.The results of the drug release kinetics study showed that the sustained drug release process of HPMC-NIPAM temperature-sensitive cellulose aerogel conformed to the Fick diffusion release law of the Korsmyer-Peppas model.(2)Based on the HPMC-NIPAM temperature-sensitive cellulose aerogel construction method,a carboxymethyl cellulose(CMC)matrix with higher charge density and carboxyl active sites was used to construct CMC/PNIPAM and CMC/Ca2+/PNIPAM cellulose-based aerogel with temperature and pH response.The network structure and drug loading performance of CMC/PNIPAM aerogels were regulated by cation Ca2+,and the effect of carboxyl active sites on drug loading and sustained release performance was studied.Modern analytical methods were used to study the microstructure and drug loading properties of NIPAM’s self-polymer PNIPAM aerogel,CMC/PNIPAM and CMC/Ca2+/PNIPAM two cellulose aerogels.The results showed that with the introduction of CMC,a semi-interpenetrating network is formed between cellulose molecules.Compared with PNIPAM aerogel,CMC/PNIPAM cellulose aerogel had significantly improved porosity,bulk density,surface charge density and compressibility.The addition of Ca2+ played a role in ionic crosslinking,and the formed CMC/Ca2+/PNIPAM cellulose aerogel had an interpenetrating network structure and more uniform pore structure.The results of exploring the adsorption behavior of 5-FU drugs showed that the drug adsorption curves of CMC/PNIPAM and CMC/Ca2+/PNIPAM two cellulose aerogels were in line with the Langmuir isotherm adsorption model,which was a single molecular layer physical adsorption.The maximum adsorption capacities were 161.33 mg/g and 199.30 mg/g,respectively,indicating that the construction of the interpenetrating network and the introduction of carboxyl groups could effectively increase the drug loading.The investigation results of the sustained release performance of the drug showed that under the same release time of 300 min,the drug release rate of CMC/PNIPAM,CMC/Ca2+/PNIPAM drug-loaded cellulose aerogel was significantly faster at 37℃ than at 25℃,and it was obviously faster at pH 3 than pH 7.4,which had good temperature and pH response performance.The sustained release process of drug-loaded cellulose aerogel also conformed to the Fick diffusion and release law of Korsmyer-Peppas model.(3)On the basis of CMC/Ca2+/PNIPAM cellulose aerogel,carbon nanotubes(CNT)and graphene oxide(GO)were introduced respectively to prepare CNT and GO hybrid CMC/Ca2+/PNIPAM cellulose aerogels with more uniform network structure.SEM,micro-CT and mercury porosimeter were used to analyze CNT and GO hybrid aerogels,the results showed that the hybridization of CNT and GO made the pore structure of CMC/Ca2+/PNIPAM cellulose aerogels more uniform and dense,and drug loading performance and sustained release performance had also been improved.Due to the more abundant active groups on the surface of GO such as carboxyl and hydroxyl groups,the obtained hybrid aerogel had a smaller average pore size;the drug-loading performance was improved to 240.59 mg/g compared with the 223.12 mg/g of the CNT hybrid aerogel,and the performance of sustained release was longer from 360 min to 480 min.It was conducive to high-efficiency loading and controllable release of drugs,which improved the utilization of drugs.