Microfluidic Synthesis of Lignin/Chitosan Nanoparticles for the pH-Responsive Delivery of Anticancer Drugs

In this work, lignin/chitosan nanoparticles (Lig/Chi NPs) with controlled structures were synthesized in a simple and scalable microfluidic system. When the positively charged chitosan and the negatively charged lignin solution were blended in a microreactor, Lig/Chi NPs were rapidly formed via the electrostatic coassembly between the amino groups of chitosan and the carboxyl groups of lignin. The zeta potential changes from negative (-13 mV) to positive (+54.5 mV) for Lig NPs and Lig/Chi NPs, respectively. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results demonstrated that Lig/Chi NPs have an average particle size of about 180 nm, which can be used as nanocarriers for drug delivery. The anticancer drug nanoparticles with docetaxel (DTX) and curcumin (CCM) were prepared by coassembly with Lig/Chi NPs in a microreactor, which had good drug loading efficiency, biocompatibility, and can release drugs in response to pH in the weakly acidic environment of the tumor. The drug release amounts in acidic solutions that simulated the tumor microenvironment were 51% (DTX@Lig/Chi NPs) and 50% (CCM@Lig/Chi NPs), respectively, which were better than the release amounts at pH 7.4, and have an obvious killing effect on HeLa cells.