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SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood-brain barriers.
J Drug Target 2011; 19(2):114-24JD

Abstract

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.

Authors+Show Affiliations

Institute of Microbiology and Hygiene, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20367080

Citation

Shubar, Hend M., et al. "SDS-coated Atovaquone Nanosuspensions Show Improved Therapeutic Efficacy Against Experimental Acquired and Reactivated Toxoplasmosis By Improving Passage of Gastrointestinal and Blood-brain Barriers." Journal of Drug Targeting, vol. 19, no. 2, 2011, pp. 114-24.
Shubar HM, Lachenmaier S, Heimesaat MM, et al. SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood-brain barriers. J Drug Target. 2011;19(2):114-24.
Shubar, H. M., Lachenmaier, S., Heimesaat, M. M., Lohman, U., Mauludin, R., Mueller, R. H., ... Liesenfeld, O. (2011). SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood-brain barriers. Journal of Drug Targeting, 19(2), pp. 114-24. doi:10.3109/10611861003733995.
Shubar HM, et al. SDS-coated Atovaquone Nanosuspensions Show Improved Therapeutic Efficacy Against Experimental Acquired and Reactivated Toxoplasmosis By Improving Passage of Gastrointestinal and Blood-brain Barriers. J Drug Target. 2011;19(2):114-24. PubMed PMID: 20367080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood-brain barriers. AU - Shubar,Hend M, AU - Lachenmaier,Sabrina, AU - Heimesaat,Markus M, AU - Lohman,Uwe, AU - Mauludin,Rachmat, AU - Mueller,Rainer H, AU - Fitzner,Rudolf, AU - Borner,Klaus, AU - Liesenfeld,Oliver, Y1 - 2010/04/01/ PY - 2010/4/7/entrez PY - 2010/4/7/pubmed PY - 2011/4/1/medline SP - 114 EP - 24 JF - Journal of drug targeting JO - J Drug Target VL - 19 IS - 2 N2 - 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. SN - 1029-2330 UR - https://www.unboundmedicine.com/medline/citation/20367080/SDS_coated_atovaquone_nanosuspensions_show_improved_therapeutic_efficacy_against_experimental_acquired_and_reactivated_toxoplasmosis_by_improving_passage_of_gastrointestinal_and_blood_brain_barriers_ L2 - http://www.tandfonline.com/doi/full/10.3109/10611861003733995 DB - PRIME DP - Unbound Medicine ER -