Formulation of two lipid-based membrane-core nanoparticles for FOLFOX combination therapy

FOLFOX is a combination of folinic acid (FnA), 5-fluorouracil (5-Fu) and oxaliplatin (OxP). It has been used as the standard treatment for colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This treatment is effective, but its high toxicity is dose limiting, and the drugs need to be taken for a long time. To lower the toxicity so that higher doses can be administered with minimal side effects, two lipid-based membrane-core (MC) nanoformulations, Nano-Folox and Nano-FdUMP, have recently been developed by using the nanoprecipitation technique. The combination of Nano-Folox (containing platinum drug and FnA) and Nano-FdUMP (containing fluorine drug) significantly improves the antitumor effect against CRC and HCC relative to FOLFOX (the combination of free drugs), resulting in long-term survival of animals without significant toxic signs. Here, we describe two formulation protocols. First, for Nano-Folox, a Pt(DACH)center dot FnA nanoprecipitate is formed by [Pt(DACH)(H2O)(2)](2+) (the active form of OxP) and FnA(2-), and the resultant nanoprecipitate is encapsulated inside the lipid nanoparticles (NPs) modified with the PEGylated aminoethyl anisamide (AEAA, a targeting ligand for sigma-1 receptor overexpressing on CRC and HCC). Second, for Nano-FdUMP, FdUMP (the active metabolite of 5-Fu) is entrapped inside the amorphous Ca-3(PO4)(2) nanoprecipitate, and the resultant Ca-3(PO4)(2)center dot FdUMP nanoprecipitate is encapsulated into the AEAA-targeted PEGylated lipid NPs. The procedures for Nano-Folox and Nano-FdUMP take similar to 17 h and similar to 4 h, respectively (similar to 17 h if they are prepared simultaneously). Procedures for the physicochemical (similar to 30 h) and cytotoxic (similar to 54 h) characterization are also described.

Automated summary

FOLFOX is an effective treatment for colorectal cancer and hepatocellular carcinoma, but its high toxicity limits the dosage. Two lipid-based nanoformulations, Nano-Folox and Nano-FdUMP, have been developed to lower toxicity and improve antitumor effect. The protocols for preparing these nanoformulations are described.