Preparation of Drug Carrier Material with Targeted and Sustained-Release from Modified Lignin

Abstract

In this paper, the modified lignin drug carrier materials with targeted slow release effect were studied. 0.2 g of alkali lignin was added to 20 mL of acetylation reagent (the ratio of acetyl bromide to acetic acid is 8:92) at 50 °C, sealed and stirred for 3 h for acetylation reaction, rotary evaporation for 30 min, drying to a fixed weight, to obtain acetylated lignin, recorded as ACAL. Dissolve 2.0 mg of ACAL in 10 mL of 99.5% ethanol solution and stir continuously at room temperature for 2 h. Deionized water is added during mixing until the desired water content is reached. After continuous stirring for 10 min, the lignin-coated material was obtained by rotating evaporation for 2 h. 5 mL prepared ACAL solution (6 mg/mL) and 5 mL prepared PTX solution (10 mg/mL) were mixed, and 0.15 V/min was dropped into deionized water magnetic force and stirred for 16 h until the final water content was 99%. The suspension was transferred to a rotary evaporator, evaporated for 2 h, and dried to constant weight to obtain the lignin/paclitaxel drug carrier system, labeled as ACAL/PTX materials. Fourier transform infrared spectroscopy (FIRS), hydrogen nuclear magnetic resonance (¹H-NMR), ultraviolet-visible spectroscopy (UV), field emission scanning electron microscopy (SEM) and Zeta potential were used to study and characterize the modified lignin drug carrier materials with targeted and sustained release. The drug release, toxicity, distribution and anticancer effect in vitro were studied. The results show that the solubility of acetylated lignin in alcohol is 1.14 times that of alkali lignin. he modified acetyl group replaced the free phenol hydroxide group in the benzene ring of lignin, and the structure of lignin itself did not change. Lignin coating material is hollow porous nanospheres, and its drug loading rate and encapsulation rate reach 17.8% and 71.23% respectively. acilitate release rate was only 21.94% when pH value of human gastric juice was 1.2. The release rate of facilitate could reach 74.81% at pH 5.5 of simulated tumor cells. Significant drug release occurred within the first 10 h. When the concentration of lignin carrier material was 10–100 mg/mL, the survival rate of cells was greater than 95%, indicating that lignin coated material was non-toxic and had stable slow-release and targeting effect. In addition, the biological distribution of facilitate in mice showed that PTX was mainly concentrated in tumor sites of mice, but 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/PTX drug delivery system has high targeting and anti-cancer effect.