Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT29 cell lines

SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan, which is 100-1000 folds more cytotoxic than irinotecan. Nonetheless extreme hydrophobicity of SN-38 has prevented its clinical use. One way of improving the solubility and stability of SN-38 is to formulate the drug into nanoparticles. Folic acid has been widely employed as a targeting moiety for various anti-cancer drugs. For folate-receptor-targeted anti-cancer therapy, SN-38 nanoparticles were produced employing poly-lactide-co-glycolide–polyethylene glycol–folate (PLGA-PEG-FOL) conjugate by emulsification/solvent evaporation method. The FOL-conjugated di-block copolymer was synthesized by coupling the PLGA-PEG-NH2 di-block copolymer with an activated folic acid. The conjugates were used for the formation of SN-38 NPs with an average size of 200 nm in diameter. The SN-38 targeted nanoparticles showed a greater cytotoxicity against HT-29 cancer cells than SN-38 non-targeted nanoparticles. These results suggested that folate-targeted nanoparticles could be a potentially useful delivery system for SN-38 as an anticancer agent.