| As a carrier that can accurately reach the target of anti-tumor drugs,improve the efficacy of drugs and reduce the toxic and side effects of drugs,drug encapsulated materials have been widely concerned in various fields.Traditional drug packaging materials are highly toxic,causing a series of neurotoxicity,drowsiness,dyspnea and other side effects.Therefore,it is necessary to develop new drug packaging materials to improve drug targeting and reduce the adverse reactions of materials.Lignin,as an important component of plant fibers,is difficult to degrade due to its large reserves and low toxicity.However,as a kind of three-dimensional network polymer compound,lignin can self-assemble into nano-hollow microporous spheres by intermolecular electrostatic attraction,which provides a possibility for the preparation of drug encapsulated materials using lignin.Therefore,in this paper,a wide range of lignin sources were used to prepare encapsulated materials with low toxicity and high release rate to improve the targeting and sustained release performance of drugs,enrich the existing encapsulated materials for drugs,and provide a way for the effective utilization of lignin.First of the alkali lignin by acetylation method modification,with acetylated lignin（ACAL）ultraviolet absorbance at 350 nm as an index,select the acetylation reagent（acetyl bromine and glacial acetic acid）of volume ratio,the temperature of the acetylation and three factors of acetylation reaction time of 3 factors 3 levels orthogonal experiments,the results show that the The volume ratio of acetyl bromide to glacial acetic acid was 8:92,and the acetylation effect was the best at 50°C for 3 h.Fourier transform infrared spectroscopy（FT-IR）and nuclear magnetic resonance hydrogen spectroscopy（~1HNMR）showed that the modified acetyl group replaced the free phenolic hydroxyl group in the benzene ring of lignin,and the structure of lignin itself did not change.The solubility of acetylated lignin in alcohol solution is 1.14times that of alkali lignin by ultraviolet and visible light analysis.Then acetylated lignin by certain rate drops and deionized water in the preparation of lignin package materials,the Zeta potential of nanoparticles as index,the selection of the initial concentration of acetylated lignin,ion water droplets acceleration and lignin carrier materials three factors of final moisture content of 3 factors 3 levels orthogonal experiments,the results show that the When the initial concentration of acetylation lignin was 6 mg/m L,the drop acceleration was 0.15 V/min and the final water content was 99%,the preparation effect of lignin-coated material was the best.Scanning electron microscopy（SEM）showed that the lignin-coated material was hollow microporous nanospheres.Then,the lignin/paclitaxel drug loading system（ACAL/PTX）was prepared by blending the lignin coated material with paclitaxel（PTX）,and the drug release,cytotoxicity,drug distribution and anticancer effect of ACAL/PTX were tested in vitro.The results of drug loading rate and encapsulation rate showed that the drug loading rate and encapsulation rate of lignin-coated materials for taxol reached 17.8%and 71.23%respectively.In vitro drug release test showed that paclitaxel release rate was only 21.94%when p H value of human gastric juice was 1.2.The release rate of paclitaxel could reach 74.81%at p H 5.5 of simulated tumor cells.The drug release behavior was obvious within 10 h.Cytotoxicity test showed that when the concentration of lignin coated material was10-100 mg/m L,the survival rate of cells was more than 95%,indicating that lignin coated material was non-toxic and had stable slow-release and targeting effect.In addition,the biological distribution of paclitaxel in mice showed that paclitaxel was mainly concentrated in tumor sites of mice,and PTX content in liver,spleen,lung and kidney was low.In the anti-cancer effect test,the tumor cells were significantly reduced after 5 consecutive administration,which also proved that the lignin/paclitaxel drug delivery system has high targeting and anti-cancer effect.In conclusion,in this study,the acetylated modified lignin drug encapsulated material was successfully prepared,and the encapsulation rate of paclitaxel reached the average level of drug encapsulated material,and the material had good targeting and sustained release performance,and the tumor growth could be successfully inhibited by the coating of paclitaxel. |
