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Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system.

Wang Z, Zhao Y, Jiang Y, Lv W, Wu L, Wang B, Lv L, Xu Q, Xin H - Sci Rep (2015)

Bottom Line: The in vivo biodistribution and near-infrared fluorescence imaging evidenced that T7 modification rendered liposomes significantly enhanced the transport of liposomes across the BBB.The pharmacodynamic study suggested that, T7-P-LPs/ZL006 exhibited reduced infarct volume and ameliorated neurological deficit compared with unmodified liposomes or free ZL006.T7-P-LPs/ZL006 could be targeted to brain and displayed remarkable neuroprotective effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

ABSTRACT
The treatment for ischemic stroke is one of the most challenging problems and the therapeutic effect remains unsatisfied due to the poor permeation of drugs across the blood brain barrier (BBB). In this study, HAIYPRH (T7), a peptide that targeted to transferrin receptor (TfR) can mediate the transport of nanocarriers across the BBB, was conjugated to liposomes for ischemic stroke targeting treatment of a novel neuroprotectant (ZL006). T7-conjugated PEGylated liposomes (T7-P-LPs) loaded with ZL006 (T7-P-LPs/ZL006) were showed satisfactory vesicle size and size distribution. Furthermore, the cellular uptake results showed that T7 modification increased liposomes uptake by the brain capillary endothelial cells (BCECs) and little cytotoxicity of liposomes with or without ZL006 was observed. The in vivo biodistribution and near-infrared fluorescence imaging evidenced that T7 modification rendered liposomes significantly enhanced the transport of liposomes across the BBB. The pharmacodynamic study suggested that, T7-P-LPs/ZL006 exhibited reduced infarct volume and ameliorated neurological deficit compared with unmodified liposomes or free ZL006. T7-P-LPs/ZL006 could be targeted to brain and displayed remarkable neuroprotective effects. They could be used as a potential targeted drug delivery system of ischemic stroke treatment.

No MeSH data available.


Related in: MedlinePlus

Cellular uptake of coumarin-6-labeled P-LPs and T7-P-LPs after incubation for 1 h at the concentrations ranged from 5 ng/mL to 500 ng/mL in BCECs (A). Cellular uptake of coumarin-6-labeled P-LPs and T7-P-LPs at different incubation time ranged from 0.25 to 6 h in BCECs at the concentration of 100 μg/mL (B). ***p < 0.001 compared with P-LPs.
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f4: Cellular uptake of coumarin-6-labeled P-LPs and T7-P-LPs after incubation for 1 h at the concentrations ranged from 5 ng/mL to 500 ng/mL in BCECs (A). Cellular uptake of coumarin-6-labeled P-LPs and T7-P-LPs at different incubation time ranged from 0.25 to 6 h in BCECs at the concentration of 100 μg/mL (B). ***p < 0.001 compared with P-LPs.

Mentions: Quantitatively, with the T7 peptide modification, the intracellular coumarin-6 intensity of T7-P-LPs was significantly higher than that of unmodified P-LPs at the concentrations ranged from 5 ng/mL to 500 ng/mL, and at the incubation time ranged from 0.25 to 6 h (Fig. 4). The quantitative analysis of cellular uptake by BCECs was also in a concentration-dependent mode within 1 h (Fig. 4A). The cellular uptake of coumarin-6-labeled T7-P-LPs was 1.34, 1.37, 1.46 and 1.42 folds higher when compared with that of P-LPs at the concentration of 5, 20, 200 and 500 ng/mL, respectively. In addition, the time-related experiment exhibited that the fluorescence intensity of coumarin-6-labeled T7-P-LPs on BCECs was significantly enhanced when compared with that of P-LPs at all experiment time points (Fig. 4B). These results indicated that T7 played an active targeting role in T7-P-LPs uptake by BCECs via transferrin receptor mediated endocytosis.


Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system.

Wang Z, Zhao Y, Jiang Y, Lv W, Wu L, Wang B, Lv L, Xu Q, Xin H - Sci Rep (2015)

Cellular uptake of coumarin-6-labeled P-LPs and T7-P-LPs after incubation for 1 h at the concentrations ranged from 5 ng/mL to 500 ng/mL in BCECs (A). Cellular uptake of coumarin-6-labeled P-LPs and T7-P-LPs at different incubation time ranged from 0.25 to 6 h in BCECs at the concentration of 100 μg/mL (B). ***p < 0.001 compared with P-LPs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4518266&req=5

f4: Cellular uptake of coumarin-6-labeled P-LPs and T7-P-LPs after incubation for 1 h at the concentrations ranged from 5 ng/mL to 500 ng/mL in BCECs (A). Cellular uptake of coumarin-6-labeled P-LPs and T7-P-LPs at different incubation time ranged from 0.25 to 6 h in BCECs at the concentration of 100 μg/mL (B). ***p < 0.001 compared with P-LPs.
Mentions: Quantitatively, with the T7 peptide modification, the intracellular coumarin-6 intensity of T7-P-LPs was significantly higher than that of unmodified P-LPs at the concentrations ranged from 5 ng/mL to 500 ng/mL, and at the incubation time ranged from 0.25 to 6 h (Fig. 4). The quantitative analysis of cellular uptake by BCECs was also in a concentration-dependent mode within 1 h (Fig. 4A). The cellular uptake of coumarin-6-labeled T7-P-LPs was 1.34, 1.37, 1.46 and 1.42 folds higher when compared with that of P-LPs at the concentration of 5, 20, 200 and 500 ng/mL, respectively. In addition, the time-related experiment exhibited that the fluorescence intensity of coumarin-6-labeled T7-P-LPs on BCECs was significantly enhanced when compared with that of P-LPs at all experiment time points (Fig. 4B). These results indicated that T7 played an active targeting role in T7-P-LPs uptake by BCECs via transferrin receptor mediated endocytosis.

Bottom Line: The in vivo biodistribution and near-infrared fluorescence imaging evidenced that T7 modification rendered liposomes significantly enhanced the transport of liposomes across the BBB.The pharmacodynamic study suggested that, T7-P-LPs/ZL006 exhibited reduced infarct volume and ameliorated neurological deficit compared with unmodified liposomes or free ZL006.T7-P-LPs/ZL006 could be targeted to brain and displayed remarkable neuroprotective effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

ABSTRACT
The treatment for ischemic stroke is one of the most challenging problems and the therapeutic effect remains unsatisfied due to the poor permeation of drugs across the blood brain barrier (BBB). In this study, HAIYPRH (T7), a peptide that targeted to transferrin receptor (TfR) can mediate the transport of nanocarriers across the BBB, was conjugated to liposomes for ischemic stroke targeting treatment of a novel neuroprotectant (ZL006). T7-conjugated PEGylated liposomes (T7-P-LPs) loaded with ZL006 (T7-P-LPs/ZL006) were showed satisfactory vesicle size and size distribution. Furthermore, the cellular uptake results showed that T7 modification increased liposomes uptake by the brain capillary endothelial cells (BCECs) and little cytotoxicity of liposomes with or without ZL006 was observed. The in vivo biodistribution and near-infrared fluorescence imaging evidenced that T7 modification rendered liposomes significantly enhanced the transport of liposomes across the BBB. The pharmacodynamic study suggested that, T7-P-LPs/ZL006 exhibited reduced infarct volume and ameliorated neurological deficit compared with unmodified liposomes or free ZL006. T7-P-LPs/ZL006 could be targeted to brain and displayed remarkable neuroprotective effects. They could be used as a potential targeted drug delivery system of ischemic stroke treatment.

No MeSH data available.


Related in: MedlinePlus