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The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of antiretroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). Severe combined immunodeficiency mice inoculated with HIV-1 infected human monocyte-derived macrophages (MDM) into the basal ganglia were treated with P85, antiretroviral therapy (ART) (zidovudine, lamivudine and nelfinavir (NEL)), or P85 and ART. Mice were killed on days 7 and 14, and brains were evaluated for levels of viral infection. Antiviral effects of NEL, P85, or their combination were evaluated in vitro using HIV-1 infected MDM and showed antiretroviral effects of P85 alone. In SCID mice injected with virus-infected MDM, the combination of ART-P85 and ART alone showed a significant decrease of HIV-1 p24 expressing MDM (25% and 33% of controls, respectively) at day 7 while P85 alone group was not different from control. At day 14, all treatment groups showed a significant decrease in percentage of HIV-1 infected MDM as compared with control. P85 alone and combined ART-P85 groups showed the most significant reduction in percentage of HIV-1 p24 expressing MDM (8% to 22% of control) that were superior to the ART alone group (38% of control). Our findings indicate major antiretroviral effects of P85 and enhanced in vivo efficacy of antiretroviral drugs when combined with P85 in a SCID mouse model of HIVE.<\/jats:p>","DOI":"10.1038\/sj.jcbfm.9600414","type":"journal-article","created":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T04:40:26Z","timestamp":1161751226000},"page":"1033-1042","source":"Crossref","is-referenced-by-count":51,"title":["Novel Delivery System Enhances Efficacy of Antiretroviral Therapy in Animal Model for HIV-1 Encephalitis"],"prefix":"10.1177","volume":"27","author":[{"given":"Timothy J","family":"Spitzenberger","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Heilman","sequence":"additional","affiliation":[{"name":"Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska, USA"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey","family":"Diekmann","sequence":"additional","affiliation":[{"name":"Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska, USA"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena V","family":"Batrakova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander V","family":"Kabanov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard E","family":"Gendelman","sequence":"additional","affiliation":[{"name":"Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska, USA"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William F","family":"Elmquist","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Persidsky","sequence":"additional","affiliation":[{"name":"Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska, USA"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical 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