Treatment of Toxocara canis infections in mice with liposome-incorporated benzimidazole carbamates and immunomodulator glucan.
Benzimidazole carbamates (mebendazole, albendazole and fenbendazole) are the most commonly used anthelmintic drugs for the treatment of larval toxocariasis (Toxocara canis) in paratenic hosts. However, the bioavailability of these drugs for tissues is very low due to their extremely low solubility, resulting in the administration of relatively high doses over a long period. To overcome this problem, neutral, negatively or positively charged and stabilized liposome drug carriers were examined in the chronic phase of T. canis infections in mice each orally inoculated with 1000 eggs. Moreover, liposomized albendazole and fenbendazole were co-administered with liposomized immunomodulator glucan. The highest efficacy of both drugs, evaluated 4 weeks after treatment, was recorded after their subcutaneous administration (ten doses of 25 mg kg(-1)) in stabilized liposomes and intramuscular co-administration of liposomized glucan (two doses of 5 mg kg(-1)). Fenbendazole was more effective in muscles (91.5%) whereas albendazole was more effective in the brain (92.2%). Liposomes with incorporated benzimidazole carbamate anthelmintics provide sustained drug-release reservoirs and can considerably enhance drug efficacy. Moreover, despite suppression by T. canis antigens, stimulation of the immune system by the immunomodulator glucan potentiates the effects of these antiparasitic drugs.
Hrckova
G
G
Parasitological Institute, The Slovak Academy of Sciences, Kosice, Slovak Republic. hrcka@saske.sk.
Velebný
S
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D015766:Albendazole / Q000008:administration & dosage; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005273:Fenbendazole / Q000008:administration & dosage; D005936:Glucans / Q000008:administration & dosage*; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008081:Liposomes; D008297:Male; D051379:Mice; D017166:Toxocara canis; D014120:Toxocariasis / Q000188:drug therapy*; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000871:Anthelmintics; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005936:Glucans; D008081:Liposomes; D005273:Fenbendazole; D015766:Albendazole