Preparation of pH-sensitive lignin nanoparticles and its application in hydrophobic drug delivery

Abstract

The majority of current oral drugs are hydrophobic, and have the toxic side effects to the gastrointestinal tract, which limit their therapeutic efficacy. In order to improve the performance of drug formulations, the development of new functional materials is crucial for the technological breakthroughs in the pharmaceutical industry. The antimicrobial and antioxidant properties of lignin nanoparticles (LNPs) give them great potential for application in this field. LNPs consist of a hydrophilic shell and hydrophobic core, which is particularly suitable for the capsulation of hydrophobic drugs, and then it would increase the stability and solubility of drugs and reduced the irritation to the stomach. In this study, alkali lignin (AL) was fractionated by 80% methanol to obtain targeted MAL with low molecular weight, high phenolic hydroxyl content and good homogeneity. The LNPs was prepared by quaternization modification of MAL and self-assembling in an ethanol/water mixture. Their application in the hydrophobic oral drug delivery system was evaluated and Ibuprofen (IBU) was used as a drug pattern. The effect of solvent exchange time (24 h, 36 h, 48 h and 60 h) on the formation process of IBU-loaded LNPs (IBU-LNPs) was investigated. The in vitro release experiments were conducted and it revealed that IBU release occurred priority in the intestine rather than the stomach, which were meeting the release requirements of ideal oral carrier. In addition, IBU-LNPs showed non-cytotoxic against the L929 cells and improved the bioavailability of IBU drugs. Therefore, this work proposes a preparation method of the smart lignin nanoparticle by screening characteristic lignin with higher reactivity and by modulating the solvent exchange time during the preparation process. Overall, LNPs showed the great potential of application in pharmaceuticals industry and was demonstrated a promising and green product.