In vivo safety and adhesion study of novel sodium alginate-chitosan microsphere with isoniazid
Objective To investigate the safety and adhesion of novel sodium alginate-chitosan microsphere with isoniazid(SCMI)in rat trachea and lung tissue.Methods A total of 24 male SD rats were randomly divided into control group(NC group),isonicotinic acid hydrazide(INH)group and SCMI group,with 8 rats in each group.The histopathological changes of liver,kidney and lung were observed by HE stained sections.The levels of inflammatory factors interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in rat alveolar lavage fluid were detected by enzyme linked immunosorbent assay.Blood white blood cell(WBC),lymphocyte(LYMPH),red blood cell(RBC),hemoglobin(Hb),platelet(PLT),aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),total bilirubin(TBiL),total protein(TSP),creatinine(Cr)and urea nitrogen(BUN)were detected.The changes of body mass in rats were observed to evaluate the safety of SCMI in rats.A total of 28 rats were given fluorescently labeled SCMI solu-tion in the trachea,the adhesion of SCMI in trachea and lung tissues was observed.Results On the 7th day after tracheal administra-tion,the body mass of rats in INH group was lower than that in NC group and SCMI group,and the differences were statistically signifi-cant(P<0.05).The expression levels of IL-1β,IL-6 and TNF-α in lung tissue of INH group were higher than those in NC group and SCMI group,and the differences were statistically significant(P<0.05).There was no significant difference in WBC,LYMPH,RBC,Hb,PLT,AST,ALT,ALP,TBiL,TSP,Cr and BUN among all groups(P>0.05).After12 hours of administration,a large number of fluorescent labels could be seen in the lung lobe tissue,suggesting that SCMI could be widely distributed in the lung lobe within 12 hours.A large number of fluorescent labels were observed at 48 hours,suggesting that SCMI could still adhere to lung lobe in large quantities after 48 hours of local administration of tracheal SCMI.Conclusion SCMI improved INH adhesion in rats and had a good safety in intratracheal administration,making it a promising vehicle for local INH delivery.
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