Codina Ana V, García Agustina, Leonardi Darío, Vasconi María D, Di Masso Ricardo J, Lamas María C, Hinrichsen Lucila I
Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2000KTR Rosario, Argentina.
IQUIR-CONICET, Suipacha 570, 2000 Rosario, Argentina; Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000 Rosario, Argentina.
Int J Biol Macromol. 2015;77:203-6. doi: 10.1016/j.ijbiomac.2015.02.049. Epub 2015 Mar 16.
Albendazole-β-cyclodextrin citrate (ABZ:C-β-CD) inclusion complex in vivo antiparasitic activity was evaluated in the parenteral phase of Trichinella spiralis infection in mice. An equimolar complex of ABZ:C-β-CD was prepared by spray-drying and tested in CBi-IGE male mice orally infected with L1 infective larvae. Infected animals were treated with 50 or 30mg/kg albendazole, (ABZ) equivalent amounts of the ABZ:C-β-CD complex and non treated (controls). Mice received a daily dose on days 28, 29 and 30 post-infection. A week later, larval burden and percentage of encysted dead larvae were assessed in the host by counting viable and non-viable larvae in the tongue. Complexation of ABZ with C-β-CD increased the drug dissolution efficiency nearly eightfold. At 37 days p-i, the reduction percentage in muscle larval load was 35% in mice treated with 50mg/kg/day ABZ and 68% in those given the complex. Treatment with the lower dose showed a similar decrease in parasite burden. Treated animals showed a high percentage of nonviable larvae, the proportion being significantly higher in mice receiving the complex than in control animals (72-88% vs. 11%, P=0.0032). These data indicate that ABZ:C-β-CD increases bioavailability and effectiveness of ABZ against encapsulated Trichinella larvae, thus allowing the use of small doses.
在小鼠旋毛虫感染的肠外期评估了阿苯达唑 -β-环糊精柠檬酸盐(ABZ:C-β-CD)包合物的体内抗寄生虫活性。通过喷雾干燥制备了ABZ:C-β-CD的等摩尔复合物,并在经L1感染性幼虫口服感染的CBi-IGE雄性小鼠中进行测试。感染动物分别用50或30mg/kg阿苯达唑(ABZ)、等量的ABZ:C-β-CD复合物进行治疗,未治疗的作为对照。小鼠在感染后第28、29和30天接受每日剂量治疗。一周后,通过计数舌部存活和非存活幼虫来评估宿主体内的幼虫负荷和包囊死亡幼虫的百分比。ABZ与C-β-CD形成包合物使药物溶解效率提高了近八倍。感染后37天,用50mg/kg/天ABZ治疗的小鼠肌肉幼虫负荷降低百分比为35%,给予复合物的小鼠为68%。较低剂量治疗也显示出寄生虫负荷有类似程度的降低。治疗的动物显示出高比例的非存活幼虫,接受复合物的小鼠中这一比例显著高于对照动物(72 - 88%对11%,P = 0.0032)。这些数据表明ABZ:C-β-CD提高了ABZ对包囊化旋毛虫幼虫的生物利用度和有效性,从而允许使用小剂量药物。