Regulated preparation of celastrol-loaded nanoparticle by flash nanoprecipitation

Active components in Chinese medicine have shown great effects in treating various illness covering inflammation, obesity, diabetes and cancer. However, most of the active components, e.g. celastrol, suffer from the poor solubility and severe toxicity which limit their practical applications. One of the promising strategies is to load drugs in polymeric nanoparticles (NPs). While so far, most of the drug-loaded NPs were prepared by anti-solvent assembly or precipitation, which is a spontaneous and time-consuming process that provides thermodynamic equilibrium NPs with typically low particle yield and drug loading content. Herein, we apply a kinetically controlled method, namely Flash Nanoprecipitation (FNP), to construct celastrol-loaded NPs. Specifically, solvent streams containing celastrol and biodegradable Dextran-b-PLGA are mixed with anti-solvent streams in a multi-inlet vortex mixer. The fast mixing and co-precipitation provide NPs with well-defined particle radius (80-160 nm, PDI <0.2) and structure, high celastrol loading content (11-63%) and tunable release as well. The regulation is achieved by manipulating the drug concentration and stream velocity (defined as Reynolds number). Moreover, the obtained NPs display efficient inhibition of A549 lung cancer cells, whereas notably reduced cytotoxicity to HL-7702 normal liver cell lines. Our study validates advantages of FNP method on preparing Chinese medicine drug-loaded NPs, and the achieved regulation on particle properties show great potential for boosting the application of Chinese medicine active components.

Automated summary

Active components in Chinese medicine have shown great potential in treating various diseases, but their poor solubility and toxicity limit their practical applications. Flash Nanoprecipitation (FNP) provides a promising method to construct drug-loaded nanoparticles with high loading content and tunable release. These nanoparticles display efficient inhibition of cancer cells while reducing cytotoxicity to normal cells.