纳米链霉素在小鼠结核病模型中治疗作用的研究

目的 对比研究链霉素纳米制剂与普通制剂--硫酸链霉素注射液在小鼠体内经肠胃外给药时的抗结核活性。方法 雌性BALB/c小鼠尾静脉感染结核分枝杆菌H₃₇Rv 1×10⁷CFU。感染后第2 d开始按照空白对照组、阳性对照组、比较对照组和纳米链霉素SM-NP BSA组、纳米链霉素SM-NP CRM组的剂量和频率分别腹腔注射给药,给药至感染后28 d。在感染的14、28、56 d分别处死每组4只小鼠进行脾、肺活菌计数。结果 SM-NP CRM组在整个实验期间的存活率是100%,SM-NP BSA组第28 d和第56 d的存活率分别为83%和75%。治疗14 d时,比较对照组小鼠脾、肺的菌量较阳性对照组大,而SM-BSA与SM-CRM组小鼠脾、肺的活菌数较阳性对照组降低;治疗4周时,各组的活菌数与2周时相比没有明显变化,但SM-NP BSA与SM-NP CRM组的脾、肺活菌数均比比较对照组低,差异有统计学意义。感染8周时,SM-NP BSA、SM-NP CRM组肺的活菌数量仍比阳性对照组小,差异有统计学意义。结论 纳米链霉素制剂SM-NP BSA、SM-NP CRM与普通链霉素注射液相比,在给药剂量与给药频率降低时,在小鼠急性结核病感染模型中表现的抗菌活性仍与阳性对照相当,值得进一步研究。

Effective treatment of tuberculosis in mice with nanoparticulated streptomycin

Objective To investigate the antituberculosis efficacy of newly developed nanoparticulate forms of streptomycin(SM) for parenteral administration in comparison with conventional preparation "streptomycin sulfate for injections".Methods SPF female BALB/c mice were infected with M.tuberculosis(H37Rv,ATCC27294,107 CFU/mouse,iv).Infected mice were treated ip as follows: Untreated(saline),5 times per week;SM sulfate USP,200 mg/kg,5 times per week(positive control);SM sulfate USP,100 mg/kg,twice weekly(comparative control);SM-NP BSA,100 mg/kg,twice weekly;SM-NP CRM,100 mg/kg,twice weekly.SM formulations were administered ip for 28 days.Four mice from each group were assessed for CFU count and organ weights on days 14,28 and 56.Results All animals survived in NP-SM CRM group,received 800 mg cumulative dose of SM,while survival rate for positive control(SM USP,cumulative 4000 mg) was 92%,and for comparative control(SM USP,total 800 mg) was 58%.Bacterial count in lungs and spleen were significantly lower(2.5~3 orders of magnitude) in NP groups.Conclusions The activity of Streptomycin,incorporated into biodegradable NP,was significantly improved in comparison to a conventional formulation using an acute murine tuberculosis infection model.It resulted in an 80% decrease of total dose of SM with an increased survival rate.