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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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Transmigration of MP-AZTTP liposomes across the blood–brain barrier (BBB) model. Apparent permeability coefficients (Papp) of MP-AZTTP transport across the BBB model as free and in magnetic liposomes. The data represents the mean ± SE of 3 independent experiments and is expressed as cm/min. Statistical analysis was performed using unpaired Student’s t-test.Abbreviations: AZTTP, azidothymidine 5’-triphosphate; MP-AZTTP, magnetic nanoparticles bound AZTTP.
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f3-ijn-5-157: Transmigration of MP-AZTTP liposomes across the blood–brain barrier (BBB) model. Apparent permeability coefficients (Papp) of MP-AZTTP transport across the BBB model as free and in magnetic liposomes. The data represents the mean ± SE of 3 independent experiments and is expressed as cm/min. Statistical analysis was performed using unpaired Student’s t-test.Abbreviations: AZTTP, azidothymidine 5’-triphosphate; MP-AZTTP, magnetic nanoparticles bound AZTTP.

Mentions: We then examined the ability of magnetic AZTTP liposomes to migrate across the artificial BBB model system under the influence of an external magnetic field. The intactness of the in vitro BBB model was established by TEER measurement. A mean TEER value of 150 to 200 ohms/cm2 cell culture insert is consistent with the formation of the BBB and was also reported earlier.26 Figure 3 represents the apparent permeability of AZTTP transported across the in vitro BBB as free AZTTP and as magnetic liposomes. The results showed that permeability of MP-AZTTP liposomes in the presence of a magnet is significantly higher than that of free AZTTP, 3.64 × 10−3 cm/min as compared to 1.28 × 10−3 cm/min respectively (P < 0.0001). Further, results show no significant effects on the TEER values of the BBB model before and after treatment with the MP-AZTTP liposomes (Table 2).


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

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

Transmigration of MP-AZTTP liposomes across the blood–brain barrier (BBB) model. Apparent permeability coefficients (Papp) of MP-AZTTP transport across the BBB model as free and in magnetic liposomes. The data represents the mean ± SE of 3 independent experiments and is expressed as cm/min. Statistical analysis was performed using unpaired Student’s t-test.Abbreviations: AZTTP, azidothymidine 5’-triphosphate; MP-AZTTP, magnetic nanoparticles bound AZTTP.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-5-157: Transmigration of MP-AZTTP liposomes across the blood–brain barrier (BBB) model. Apparent permeability coefficients (Papp) of MP-AZTTP transport across the BBB model as free and in magnetic liposomes. The data represents the mean ± SE of 3 independent experiments and is expressed as cm/min. Statistical analysis was performed using unpaired Student’s t-test.Abbreviations: AZTTP, azidothymidine 5’-triphosphate; MP-AZTTP, magnetic nanoparticles bound AZTTP.
Mentions: We then examined the ability of magnetic AZTTP liposomes to migrate across the artificial BBB model system under the influence of an external magnetic field. The intactness of the in vitro BBB model was established by TEER measurement. A mean TEER value of 150 to 200 ohms/cm2 cell culture insert is consistent with the formation of the BBB and was also reported earlier.26 Figure 3 represents the apparent permeability of AZTTP transported across the in vitro BBB as free AZTTP and as magnetic liposomes. The results showed that permeability of MP-AZTTP liposomes in the presence of a magnet is significantly higher than that of free AZTTP, 3.64 × 10−3 cm/min as compared to 1.28 × 10−3 cm/min respectively (P < 0.0001). Further, results show no significant effects on the TEER values of the BBB model before and after treatment with the MP-AZTTP liposomes (Table 2).

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.

Show MeSH