scholarly journals GF120918, a P-Glycoprotein Modulator, Increases the Concentration of Unbound Amprenavir in the Central Nervous System in Rats

2002 ◽  
Vol 46 (7) ◽  
pp. 2284-2286 ◽  
Author(s):  
Jeffrey E. Edwards ◽  
Kenneth R. Brouwer ◽  
Patrick J. McNamara
Keyword(s):  
Central Nervous System ◽  
Human Immunodeficiency Virus ◽  
Nervous System ◽  
Protease Inhibitors ◽  
Extracellular Fluid ◽  
Human Immunodeficiency Virus Protease ◽  
P Glycoprotein ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
The Brain

ABSTRACT The goal of this study was to determine the distribution of unbound amprenavir in the central nervous system (CNS) of rats. The concentration of unbound amprenavir in the extracellular fluid of the brain and the blood was examined in the presence and absence of the MDR modulator GF120918 by microdialysis. The brain-to-blood ratio of amprenavir in the absence and presence of GF120918 was found to be significantly different (P < 0.003; 0.076 and 0.617, respectively). The use of the MDR modulator GF120918 could potentially increase the penetration of human immunodeficiency virus protease inhibitors into the CNS.

scholarly journals Enhanced Mucosal Immunoglobulin A Response of Intranasal Adenoviral Vector Human Immunodeficiency Virus Vaccine and Localization in the Central Nervous System

2003 ◽  
Vol 77 (18) ◽  
pp. 10078-10087 ◽  
Author(s):  
Franck Lemiale ◽  
Wing-pui Kong ◽  
Levent M. Akyürek ◽  
Xu Ling ◽  
Yue Huang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Human Immunodeficiency Virus ◽  
Nervous System ◽  
Viral Vector ◽  
Recombinant Adenovirus ◽  
Immunoglobulin A ◽  
Retrograde Transport ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
Hiv 1

ABSTRACT Replication-defective adenovirus (ADV) vectors represent a promising potential platform for the development of a vaccine for AIDS. Although this vector is typically administered intramuscularly, it would be desirable to induce mucosal immunity by delivery through alternative routes. In this study, the immune response and biodistribution of ADV vectors delivered by different routes were evaluated. ADV vectors expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pol, and Env were delivered intramuscularly or intranasally into mice. Intranasal immunization induced greater HIV-specific immunoglobulin A (IgA) responses in mucosal secretions and sera than in animals with intramuscular injection, which showed stronger systemic cellular and IgG responses. Administration of the vaccine through an intranasal route failed to overcome prior ADV immunity. Animals exposed to ADV prior to vaccination displayed substantially reduced cellular and humoral immune responses to HIV antigens in both groups, though the reduction was greater in animals immunized intranasally. This inhibition was partially overcome by priming with a DNA expression vector expressing HIV-1 Gag, Pol, and Env before boosting with the viral vector. Biodistribution of recombinant adenovirus (rADV) vectors administered intranasally revealed infection of the central nervous system, specifically in the olfactory bulb, possibly via retrograde transport by olfactory neurons in the nasal epithelium, which may limit the utility of this route of delivery of ADV vector-based vaccines.

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