Conjugation of Succinate to Chitosan Increases the Cochlear Cytoprotective Effect

Abstract

N-Succinylchitosan (SC) with degree of substitution 0.86 was prepared by reacting chitosan with succinic anhydride. The otoprotective potential of a single i.v. injection of a solution (0.3%) of the sodium salt of SC in 60 rats (males, Wistar, 220 – 250 g) was studied. A solution of meglumine sodium succinate (MSS) at an equivalent concentration was used as a reference. The drugs were administered 2 h or 5 min prior to induction of acute injury of the auditory analyzer by acoustic stimulation (AS). The condition of hearing was estimated by studying optoacoustic emission (OAE) at the frequency of distortion product 1 h, 24 h, and 7 d after the AS. SC showed a more pronounced protective effect with early preventive administration (p < 0.02; ANOVA with Bonferroni correction). Conversely, MSS exhibited its protective properties only with immediate administration. A comparison of the two drug administration modes showed that the OAE amplitude was depressed more after MSS administration than after SC injection (p < 0.05; Tukey’s test). It was concluded that conjugation to chitosan prolonged the elimination half-life of succinate and improved its access to cochlear back-barrier tissues.