Randomly 50% N-acetylated low molecular weight chitosan as a novel renal targeting carrier

Selective targeting of drugs to kidneys may improve renal effectiveness and reduce extrarenal toxicity. Using fluorescence imaging, we found for the first time that randomly 50% N-acetylated low molecular weight chitosan ( LMWC) selectively accumulated in the kidneys, especially in the renal tubules after i.v. injection in mice. To develop and evaluate the novel renal drug carrier, prednisolone, used as a model drug, was covalently coupled with various molecular weight LMWCs via a succinic acid spacer. The mean residence time ( MRT) in plasma of prednisolone conjugates increased as the molecular weight increased. The conjugate with molecular weight 19kD ( conjugate-19k) displayed the highest accumulation rate in the kidneys, which was 14.06 +/- 2.81% of the administered dose 15 min after i.v. injection. The total amount of the conjugate-19k in the kidneys was 13- fold higher than that of controlled prednisolone group. Both conjugate-19k and conjugate- 31k had higher retention and about 10% of injected dose was still retained in the kidneys after 120 min. Additionally, MTT assay showed LMWCs were noncytotoxic towards L929 and NRK-52E cells. Conclusion can be drawn that the coupling of prednisolone to the proper molecular weight LMWC results in increased prednisolone concentration in the kidneys. Therefore, LMWC with a proper molecular weight can be applied as a promising carrier for renal targeting.