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Treatment of acute experimental toxoplasmosis with investigational poloxamers
J L Krahenbuhl1, Y Fukutomi, L Gu
1Immunology Research Department, G. W. Long Hansen's Disease Center, Carville, Louisiana 70721.
Abstract:
Because of the limited chemotherapeutic approaches available to treat reactivated latent Toxoplasma gondii infection manifested as toxoplasmic encephalitis in AIDS patients, investigation of novel chemotherapeutic agents is warranted. Several poloxamers (nonionic block copolymers composed of a central hydrophobic chain of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene) were tested for their abilities to alter the course of acute infection with a highly virulent T. gondii in mice. The effect varied markedly with the length of the constituent chains of the copolymers. The most effective preparations were highly effective when administered after infection and afforded remarkable protection against 10 to 1,000 100% lethal doses of T. gondii. Protection was dose dependent, and multiple treatments were more effective than single treatment. These preliminary findings warrant additional studies to determine whether this novel form of antitoxoplasma chemotherapy may prove promising in the treatment or prevention of acute toxoplasmic encephalitis in humans.
Insights
Novel poloxamer compounds show significant promise in protecting mice against severe Toxoplasma gondii infections. These findings could lead to new treatments for toxoplasmic encephalitis in immunocompromised individuals.
Area of Science:
- Immunology
- Pharmacology
- Infectious Diseases
Background:
- Limited chemotherapeutic options exist for reactivated latent Toxoplasma gondii infections, particularly toxoplasmic encephalitis in AIDS patients.
- Toxoplasmic encephalitis poses a significant threat to immunocompromised individuals due to opportunistic infections.
Purpose of the Study:
- To investigate the efficacy of poloxamers as novel chemotherapeutic agents against Toxoplasma gondii infection.
- To evaluate the protective effects of different poloxamer formulations in a murine model of acute toxoplasmosis.
Main Methods:
- Various poloxamers, nonionic block copolymers, were administered to mice infected with a virulent strain of T. gondii.
- Protection against lethal doses of T. gondii was assessed based on poloxamer formulation and treatment regimen.
Main Results:
- Poloxamer efficacy varied significantly based on the length of their polyoxypropylene and polyoxyethylene chains.
- The most effective poloxamers provided remarkable protection when administered post-infection against 10 to 1,000 lethal doses.
- Protection was dose-dependent, with multiple treatments proving more effective than single doses.
Conclusions:
- Poloxamers demonstrate significant potential as a novel antitoxoplasma chemotherapy.
- Further research is warranted to explore poloxamers for treating or preventing acute toxoplasmic encephalitis in humans.
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