Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?
Although several viruses can easily infect the central nervous system (CNS), antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs). These transporters, located in the physiological barriers betwee...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-03-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/10/2/39 |
| _version_ | 1818034983146618880 |
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| author | Alessandro Dalpiaz Barbara Pavan |
| author_facet | Alessandro Dalpiaz Barbara Pavan |
| author_sort | Alessandro Dalpiaz |
| collection | DOAJ |
| description | Although several viruses can easily infect the central nervous system (CNS), antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs). These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1), multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5), and breast cancer resistance protein (ABCG2 or BCRP). Inhibitors of AETs may be considered, but their co-administration causes serious unwanted effects. Nasal administration of antiviral drugs is therefore proposed in order to overcome the aforementioned problems, but innovative devices, formulations (thermoreversible gels, polymeric micro- and nano-particles, solid lipid microparticles, nanoemulsions), absorption enhancers (chitosan, papaverine), and mucoadhesive agents (chitosan, polyvinilpyrrolidone) are required in order to selectively target the antiviral drugs and, possibly, the AET inhibitors in the CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the AET systems, appearing as interesting substrates for innovative nasal formulations able to target anti-Human Immunodeficiency Virus (HIV) agents into macrophages of the CNS, which are one of the most important HIV Sanctuaries of the body. |
| first_indexed | 2024-12-10T06:47:49Z |
| format | Article |
| id | doaj.art-7a8b1597c93441c2a6284fb5b42d1ed5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-12-10T06:47:49Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7a8b1597c93441c2a6284fb5b42d1ed52022-12-22T01:58:37ZengMDPI AGPharmaceutics1999-49232018-03-011023910.3390/pharmaceutics10020039pharmaceutics10020039Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?Alessandro Dalpiaz0Barbara Pavan1Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, ItalyAlthough several viruses can easily infect the central nervous system (CNS), antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs). These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1), multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5), and breast cancer resistance protein (ABCG2 or BCRP). Inhibitors of AETs may be considered, but their co-administration causes serious unwanted effects. Nasal administration of antiviral drugs is therefore proposed in order to overcome the aforementioned problems, but innovative devices, formulations (thermoreversible gels, polymeric micro- and nano-particles, solid lipid microparticles, nanoemulsions), absorption enhancers (chitosan, papaverine), and mucoadhesive agents (chitosan, polyvinilpyrrolidone) are required in order to selectively target the antiviral drugs and, possibly, the AET inhibitors in the CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the AET systems, appearing as interesting substrates for innovative nasal formulations able to target anti-Human Immunodeficiency Virus (HIV) agents into macrophages of the CNS, which are one of the most important HIV Sanctuaries of the body.http://www.mdpi.com/1999-4923/10/2/39active efflux transporterantiretroviral drugHIV sanctuariesthermoreversible gelnano-emulsionpolymeric microparticlespolymeric nanoparticlesnasal formulationsolid lipid microparticlesvirus |
| spellingShingle | Alessandro Dalpiaz Barbara Pavan Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux? Pharmaceutics active efflux transporter antiretroviral drug HIV sanctuaries thermoreversible gel nano-emulsion polymeric microparticles polymeric nanoparticles nasal formulation solid lipid microparticles virus |
| title | Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux? |
| title_full | Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux? |
| title_fullStr | Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux? |
| title_full_unstemmed | Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux? |
| title_short | Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux? |
| title_sort | nose to brain delivery of antiviral drugs a way to overcome their active efflux |
| topic | active efflux transporter antiretroviral drug HIV sanctuaries thermoreversible gel nano-emulsion polymeric microparticles polymeric nanoparticles nasal formulation solid lipid microparticles virus |
| url | http://www.mdpi.com/1999-4923/10/2/39 |
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