Abstract:

Objective: The effects of enzymatic hydrolysis lignin(EHL)mass concentration in tetrahydrofuran(THF)on the structure of lignin hollow nanoparticles(LHNPs)and the effects of the structure of doxorubicin hydrochloride(DOX)loaded LHNPs(DOX@LHNPs)on the drug controlled release behavior were investigated in this study, which might provide bases for selecting entrapment utilization of LHNPs in different fields. Method: LHNPs were prepared with dissolving different quality of EHL in THF and afterward dropping deionized water to the solution. EHL could be self-assembled into nanoparticles and loaded DOX- iniside LHNPs forming drug-loaded nanoparticles, by adding a certain quality of DOX to the mixed solution. The microstructure and particle size of the material were characterized by transmission electron microscope(TEM), scanning electron microscope(SEM), laser particle size analyzer(DLS)and surface area and a pore volume analyzer. Ultraviolet-visible spectrophotometer(UV-vis), X-ray diffractometer(XRD) and infrared spectrometer(FTIR)were performed to quantify the encapsulation and controlled release of DOX by LHNPs. Result: The value obtained by DLS showed that an increase of the pre-dropping lignin mass concentration from 0.3 to 3 mg·mL^-1 led to the nanoparticles size decreased from 552.6 to 266.8 nm, whereas the PDI values were basically stable. Additionally, the distribution for size of nanoparticles was uniform, which could be stored in water for more than 10 days. Moreover, the size of shells, surface area and pore volume were also decreased with the increase of pre-dropping lignin mass concentration. Hollow spherical structure of lignin nanoparticles with a hole on the surface was observed by TEM and SEM. The test result of UV-vis, XRD and FTIR showed that DOX could be loaded by LHNPs. The behaviors of DOX release were different in two pH systems. For the same test object, the drug released slightly rapidly in acidic(pH=5.5)condition comparing with in neutral(pH=7.4)condition. The larger specific surface area and porosity could improve the encapsulation ability of hollow nanoparticles for DOX, and the thicker shell particles had more stable controlled release result for DOX. Conclusion: The EHL could be microphase-separated in tetrahydrofuran and self-assembled into a dimensionally stable nano-scale surface with hollow spherical particles of a single pore. By controlling the initial mass concentration of lignin, it might be possible to obtain hollow particles of different diameters and shell wall thicknesses. For DOX@LHNPs, the larger the area and porosity is, the greater the drug loading. However, the hollow drug-loaded nanoparticles with more regular structure and thicker shell walls were beneficial to the stable release of DOX.

Key words: enzymatic hydrolysis lignin, lignin nanoparticles, structure, doxorubicin hydrochloride