Magnetic nanoformulation of azidothymidine 5’-triphosphate for targeted delivery across the blood–brain barrier
Zainulabedin M Saiyed, Nimisha H Gandhi, Madhavan PN Nair1Department of Immunology, College of Medicine, Florida International University, Miami, FL, USAAbstract: Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly at...
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| Autores principales: | , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2010
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| Acceso en línea: | https://doaj.org/article/4441a7a6a591440382a44a2740a16f26 |
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| Sumario: | Zainulabedin M Saiyed, Nimisha H Gandhi, Madhavan PN Nair1Department of Immunology, College of Medicine, Florida International University, Miami, FL, USAAbstract: Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood–brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5’-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS.Keywords: AZTTP, magnetic liposomes, HIV-1 infectivity, transendothelial migration, blood–brain barrier |
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