Docetaxel-loaded ultrasmall nanostructured lipid carriers for cancer therapy: in vitro and in vivo evaluation

Lack of cancer-targeted delivery of chemotherapeutics is one of the major obstacles for successful cancer therapy. Nanostructured lipid carriers (NLC) have shown great promise in drug-delivery applications since they are highly scalable, biodegradable nanocarriers with high-drug-loading capacity. However, traditional method prepared NLC, the diameter of which range from 80 to 200 nm, is easily blocked and trapped in perivascular regions without further penetration. As a result, ultrasmall NLC with size under 100 nm or lower range are reported to be ideally tumor targeting carrier as it allows for superior tumor accumulation and permeation. Moreover, surface modification of NLC with folic acid (FA) could significantly increase the drug-delivery efficiency through active targeting effect. In our study, an ultrasmall NLC with FA modification (FA-NLC) was prepared to load docetaxel (DTX) for cancer therapy. Our results showed that DTX-loaded FA-NLC comprised of homogeneous particles with size around 30 nm. In addition, it exhibited great colloidal stability, satisfactory drug-loading efficiency, and high biocompatibility in vitro. Meanwhile, in vivo studies indicated that ultrasmall FA-NLC exhibited greater tumor retention and enhanced antitumor effect compared with control.