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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-12-22
pubmed:abstractText
Toxoplasmic encephalitis (TE) is the most common clinical manifestation of reactivated infection with Toxoplasma gondii in immunocompromised patients that is lethal if untreated. The combination of pyrimethamine plus sulfadiazine or clindamycin is the standard therapy for the treatment of TE, but these combinations are associated with hematologic toxicity and/or life-threatening allergic reactions. Therefore, alternative treatment options are needed. Atovaquone is safe and highly effective against T. gondii in vitro, but the oral micronized solution shows poor bioavailability. We synthesized atovaquone nanosuspensions (ANSs) coated with poloxamer 188 (P188) and sodium dodecyl sulfate (SDS) to improve oral bioavailability and passage through the blood-brain barrier (BBB). Coating of ANSs with SDS resulted in enhanced oral bioavailability and enhanced brain uptake of atovaquone compared to Wellvone(®) in murine models of acute and reactivated toxoplasmosis as measured by high performance liquid chromatography (HPLC). Parasite loads and inflammatory changes in brains of mice treated with SDS-coated ANS were significantly reduced compared to untreated controls and to Wellvone(®)-treated mice. In conclusion, nanosuspensions coated with SDS may ultimately lead to improvements in the treatment of TE and other cerebral diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1029-2330
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
114-24
pubmed:meshHeading
pubmed-meshheading:20367080-Administration, Oral, pubmed-meshheading:20367080-Animals, pubmed-meshheading:20367080-Antiprotozoal Agents, pubmed-meshheading:20367080-Atovaquone, pubmed-meshheading:20367080-Biological Availability, pubmed-meshheading:20367080-Brain, pubmed-meshheading:20367080-Chromatography, High Pressure Liquid, pubmed-meshheading:20367080-Disease Models, Animal, pubmed-meshheading:20367080-Excipients, pubmed-meshheading:20367080-Mice, pubmed-meshheading:20367080-Nanoparticles, pubmed-meshheading:20367080-Poloxamer, pubmed-meshheading:20367080-Sodium Dodecyl Sulfate, pubmed-meshheading:20367080-Suspensions, pubmed-meshheading:20367080-Tissue Distribution, pubmed-meshheading:20367080-Toxoplasma, pubmed-meshheading:20367080-Toxoplasmosis, Animal, pubmed-meshheading:20367080-Toxoplasmosis, Cerebral
pubmed:year
2011
pubmed:articleTitle
SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood-brain barriers.
pubmed:affiliation
Institute of Microbiology and Hygiene, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't