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Magnetic nanoformulation of azidothymidine 5'-triphosphate for targeted delivery across the blood-brain barrier.

Saiyed ZM, Gandhi NH, Nair MP - Int J Nanomedicine (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, College of Medicine, Florida International University, Miami, FL, USA.

ABSTRACT
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.

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Uptake of magnetic liposomes by human monocytes. Monocytes were co-cultured with rDHPE-magnetic liposomes for 2 and 4 hours and their intracellular localization was assessed by fluorescence microscopy (Zeiss, Germany). Engulfed magnetic liposomes can be visualized as red fluorescence located within the cell cytoplasm.
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f4-ijn-5-157: Uptake of magnetic liposomes by human monocytes. Monocytes were co-cultured with rDHPE-magnetic liposomes for 2 and 4 hours and their intracellular localization was assessed by fluorescence microscopy (Zeiss, Germany). Engulfed magnetic liposomes can be visualized as red fluorescence located within the cell cytoplasm.

Mentions: Previous studies have attempted to use monocytes/macrophages as cell based drug delivery carriers.13,14,27–29 In this experiment, we evaluated the ability of human monocytes to phagocytose magnetic liposomes. We co-cultured human monocytes in the presence of rhodamine labeled magnetic liposomes (Rho-ML) for 2- and 4-hour time intervals. As shown in Figure 4 the rhodamine fluorescence increased with incubation time. At 4 hours of incubation, most of the fluorescence was associated with monocytes indicating that >90% of monocytes had taken up Rho ML.


Magnetic nanoformulation of azidothymidine 5'-triphosphate for targeted delivery across the blood-brain barrier.

Saiyed ZM, Gandhi NH, Nair MP - Int J Nanomedicine (2010)

Uptake of magnetic liposomes by human monocytes. Monocytes were co-cultured with rDHPE-magnetic liposomes for 2 and 4 hours and their intracellular localization was assessed by fluorescence microscopy (Zeiss, Germany). Engulfed magnetic liposomes can be visualized as red fluorescence located within the cell cytoplasm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865010&req=5

f4-ijn-5-157: Uptake of magnetic liposomes by human monocytes. Monocytes were co-cultured with rDHPE-magnetic liposomes for 2 and 4 hours and their intracellular localization was assessed by fluorescence microscopy (Zeiss, Germany). Engulfed magnetic liposomes can be visualized as red fluorescence located within the cell cytoplasm.
Mentions: Previous studies have attempted to use monocytes/macrophages as cell based drug delivery carriers.13,14,27–29 In this experiment, we evaluated the ability of human monocytes to phagocytose magnetic liposomes. We co-cultured human monocytes in the presence of rhodamine labeled magnetic liposomes (Rho-ML) for 2- and 4-hour time intervals. As shown in Figure 4 the rhodamine fluorescence increased with incubation time. At 4 hours of incubation, most of the fluorescence was associated with monocytes indicating that >90% of monocytes had taken up Rho ML.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, College of Medicine, Florida International University, Miami, FL, USA.

ABSTRACT
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.

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