Development of liver-specific ribavirin-loaded nanoparticles with reduced cytotoxicity

Ribavirin is widely used in several types of combination chemotherapy for the treatment of chronic hepatitis C. In order to deliver ribavirin to the liver and reduce its side effects, we previously prepared ribavirin monophosphate (RMP)-loaded nanoparticles consisting of a mixture of poly(D,L-lactic acid), arabinogalactan-poly(L-lysine) conjugate, and iron (III) ions. In this study, the nanoparticles were developed in the absence of poly(L-lysine) to avoid cytotoxicity. The nanoparticles were successfully prepared from a mixture of poly(D,L-lactic acid) with terminal amino group(s) and arabinogalactan-poly(L-glutamic acid) conjugate. RMP was stably loaded in the nanoparticles and was gradually released from the nanoparticles under physiological conditions. Furthermore, high accumulation of the nanoparticles in hepatic cells was observed in vitro and in vivo. The nanoparticles also exhibited significantly lower cytotoxicity than that exhibited by those containing poly(L-lysine). Thus, the nanoparticles are expected to be useful in liver-specific ribavirin delivery with low cytotoxicity for the treatment of chronic hepatitis C.