Oligo-peptides, including monomeric amino acids, have received much attention as bioactive molecules and drugs. One of the biggest problems of these compounds, however, is their very short bioavailability due to instant metabolism and rapid excretion. To solve this problem, we newly designed a poly(ethylene glycol) (PEG)-block-polypeptide self-assembling based drug for the treatment of acute liver injury. Here, PEG-block-poly(L-Ornithine) (PEG-b-POrn) was synthesized via a ring opening polymerization, and a nano-sized polyion self-assembling complex (Nano) was prepared by simply mixing polycationic PEG-b-POrn with polyanionic chondroitin sulfate. The obtained Nano was quite stable under high ionic strength and different pH conditions and Nano exhibited extremely low toxicity in vitro and in vivo as compared to the original PEG-b-POrn. As compared to monomeric L-ornithine, administration of Nano to mice significantly improved bioavailability of liberated ornithine, especially in the liver. Interestingly, Nano treatment in acetaminophen (APAP)-induced acute liver injury mice remarkably suppressed blood ammonia levels and liver injury markers, resulting in more effective improvement of liver damage compared to monomeric ornithine via activation of ornithine transcarbomylase. These results show that the self-assembling polypeptide Nano may provide a new concept and promising therapeutics as nanomedicines.
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| http://dx.doi.org/10.1016/j.jconrel.2019.08.011 | DOI Listing |
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