Pacheco P A, Rodrigues L N C, Ferreira J F S, Gomes A C P, Veríssimo C J, Louvandini H, Costa R L D, Katiki L M
Instituto de Zootecnia (IZ/APTA/SAA), Rua Heitor Penteado, 56, Nova Odessa, SP, CEP 13.460-000, Brazil.
Universidade Federal de São Paulo (ICAQF/UNIFESP), Diadema, SP, Brazil.
Parasitol Res. 2018 Mar;117(3):705-712. doi: 10.1007/s00436-017-5740-3. Epub 2018 Jan 11.
Albendazole (ABZ), a benzimidazole widely used to control gastrointestinal parasites, is poorly soluble in water, resulting in variable and incomplete bioavailability. This has favored the appearance ABZ-resistant nematodes and, consequently, an increase in its clinical ineffectiveness. Among the pharmaceutical techniques developed to increase drug efficacy, cyclodextrins (CDs) and other polymers have been extensively used with water-insoluble pharmaceutical drugs to increase their solubility and availability. Our objective was to prepare ABZ formulations, including β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD), associated or not to the water-soluble polymer polyvinylpyrrolidone (PVP). These formulations had their solubility and anthelmintic effect both evaluated in vitro. Also, their anthelmintic efficacy was evaluated in lambs naturally infected with gastrointestinal nematodes (GIN) through the fecal egg count (FEC) reduction test. In vitro, the complex ABZ/HPβCD had higher solubility than ABZ/βCD. The addition of PVP to the complexes increased solubility and dissolution rates more effectively for ABZ/HPβCD than for ABZ/βCD. In vivo, 48 lambs naturally infected with GIN were divided into six experimental groups: control, ABZ, ABZ/βCD, ABZ/βCD-PVP, ABZ/HPβCD, and ABZ/HPβCD-PVP. Each treated animal received 10 mg/kg of body weight (based on the ABZ dose) for three consecutive days. After 10 days of the last administered dose, treatment efficacy was calculated. The efficacy values were as follows: ABZ (70.33%), ABZ/βCD (85.33%), ABZ/βCD-PVP (82.86%), ABZ/HPβCD (78.37%), and ABZ/HPβCD-PVP (43.79%). In vitro, ABZ/HPβCD and ABZ/HPβCD-PVP had high solubility and dissolution rates. In vivo, although the efficacies of ABZ/βCD, ABZ/βCD-PVP, and ABZ/HPβCD increased slightly when compared to pure ABZ, this increase was not significant (P > 0.05).
阿苯达唑（ABZ）是一种广泛用于控制胃肠道寄生虫的苯并咪唑类药物，其在水中溶解度低，导致生物利用度可变且不完全。这助长了对阿苯达唑耐药的线虫的出现，进而导致其临床疗效降低。在为提高药物疗效而开发的制药技术中，环糊精（CDs）和其他聚合物已被广泛用于与水不溶性药物结合，以提高其溶解度和可用性。我们的目标是制备包含β-环糊精（βCD）或羟丙基-β-环糊精（HPβCD）且与水溶性聚合物聚乙烯吡咯烷酮（PVP）结合或不结合的阿苯达唑制剂。对这些制剂的溶解度和驱虫效果进行了体外评估。此外，通过粪便虫卵计数（FEC）减少试验，在自然感染胃肠道线虫（GIN）的羔羊中评估了它们的驱虫效果。在体外，阿苯达唑/HPβCD复合物的溶解度高于阿苯达唑/βCD复合物。对于阿苯达唑/HPβCD复合物，添加PVP比阿苯达唑/βCD复合物更有效地提高了溶解度和溶解速率。在体内，将48只自然感染GIN的羔羊分为六个实验组：对照组、阿苯达唑组、阿苯达唑/βCD组、阿苯达唑/βCD-PVP组、阿苯达唑/HPβCD组和阿苯达唑/HPβCD-PVP组。每只接受治疗的动物连续三天接受10mg/kg体重（基于阿苯达唑剂量）的药物。在最后一次给药后10天，计算治疗效果。疗效值如下：阿苯达唑（70.33%）、阿苯达唑/βCD（85.33%）、阿苯达唑/βCD-PVP（82.86%）、阿苯达唑/HPβCD（78.37%）和阿苯达唑/HPβCD-PVP（43.79%）。在体外，阿苯达唑/HPβCD和阿苯达唑/HPβCD-PVP具有高溶解度和溶解速率。在体内，尽管与纯阿苯达唑相比，阿苯达唑/βCD、阿苯达唑/βCD-PVP和阿苯达唑/HPβCD的疗效略有提高，但这种提高并不显著（P＞0.05）。
