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Rescuing apoptotic neurons in Alzheimer's disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin.

Kuo YC, Lin CC - Int J Nanomedicine (2015)

Bottom Line: An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR.In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility.WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China.

ABSTRACT
Liposomes with cardiolipin (CL) and wheat germ agglutinin (WGA) were developed to permeate the blood-brain barrier and treat Alzheimer's disease. WGA-conjugated and CL-incorporated liposomes (WGA-CL-liposomes) were used to transport nerve growth factor (NGF) and curcumin (CUR) across a monolayer of human brain-microvascular endothelial cells regulated by human astrocytes and to protect SK-N-MC cells against apoptosis induced by β-amyloid1-42 (Aβ(1-42)) fibrils. An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR. In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility. WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.

No MeSH data available.


Related in: MedlinePlus

(A) Immunochemical staining images of WGA-CL-NGF-CUR-liposomes interacting with HBMECs. (a–d) CL-NGF-CUR-liposomes; (e–h) WGA-CL-NGF-CUR-liposomes; (a) rCL =0%; (b) rCL =5%; (c) rCL =10%; (d) rCL =20%; (e) CWGA =2.5 mg/mL and rCL =10%; (f) CWGA =2.5 mg/mL and rCL =20%; (g) CWGA =5 mg/mL and rCL =10%; (h) CWGA =5 mg/mL and rCL =20%. Green WGA-CL-NGF-CUR-liposomes are adjacent to red O-linked N-acetylglucosamine near blue HBMEC nuclei. (B) Fluorescent images of WGA-CL-NGF-CUR-liposomes interacting with SK-N-MC cells with an insult of Aβ1–42. (a) Control; (b–e) CL-NGF-CUR-liposomes; (b) rCL =0%; (c) rCL =5%; (d) rCL =10%; (e) rCL =20%; (f) CWGA =5 mg/mL, rCL =10%; (g) CWGA =5 mg/mL, rCL =20%. The Aβ1–42 concentration is 10 μM. Green WGA-CL-NGF-CUR-liposomes attached on red Aβ1–42, which is deposited near blue SK-N-MC cell nuclei.Abbreviations:CWGA, WGA concentration in grafting medium (mg/mL); rCL, CL mole percentage in lipids (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin; HBMECs, human brain-microvascular endothelial cells; Aβ1–42, β-amyloid1–42.
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f10-ijn-10-2653: (A) Immunochemical staining images of WGA-CL-NGF-CUR-liposomes interacting with HBMECs. (a–d) CL-NGF-CUR-liposomes; (e–h) WGA-CL-NGF-CUR-liposomes; (a) rCL =0%; (b) rCL =5%; (c) rCL =10%; (d) rCL =20%; (e) CWGA =2.5 mg/mL and rCL =10%; (f) CWGA =2.5 mg/mL and rCL =20%; (g) CWGA =5 mg/mL and rCL =10%; (h) CWGA =5 mg/mL and rCL =20%. Green WGA-CL-NGF-CUR-liposomes are adjacent to red O-linked N-acetylglucosamine near blue HBMEC nuclei. (B) Fluorescent images of WGA-CL-NGF-CUR-liposomes interacting with SK-N-MC cells with an insult of Aβ1–42. (a) Control; (b–e) CL-NGF-CUR-liposomes; (b) rCL =0%; (c) rCL =5%; (d) rCL =10%; (e) rCL =20%; (f) CWGA =5 mg/mL, rCL =10%; (g) CWGA =5 mg/mL, rCL =20%. The Aβ1–42 concentration is 10 μM. Green WGA-CL-NGF-CUR-liposomes attached on red Aβ1–42, which is deposited near blue SK-N-MC cell nuclei.Abbreviations:CWGA, WGA concentration in grafting medium (mg/mL); rCL, CL mole percentage in lipids (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin; HBMECs, human brain-microvascular endothelial cells; Aβ1–42, β-amyloid1–42.

Mentions: Figure 10A shows immunochemical staining images of binding and uptake of WGA-CL-NGF-CUR-liposomes by HBMECs via N-acetylglucosamine expressed on the cell membrane. As seen in Figure 10A(a–d), HBMECs expressed abundant N-acetylglucosamine moieties. In addition, a few CL-NGF-CUR-liposomes emerged around the HBMECs. Although the interaction between CL-NGF-CUR-liposomes and HBMECs was weak, there was some permeability of NGF across HBMEC/HA. The green intensity ratios in Figure 10Aa to d, Figure 10Ab to d, and Figure 10Ac to d were 1.18, 0.87, and 0.92, respectively. Thus, the green intensity in Figure 10Aa–d was at a similar level. As shown in Figure 10Ae–h, internalization of WGA-CL-NGF-CUR-liposomes by HBMECs was prevalent owing to the recognition of N-acetylglucosamine. Moreover, the green intensity in Figure 10Ae was 0.95 times that in Figure 10Af. Based on Figure 10Ah, the green intensity in Figure 10Ag is 0.92 times that in Figure 10Ah. Further, an increase in WGA concentration enhanced the uptake quantity, suggesting that WGA on the surface of WGA-CL-NGF-CUR-liposomes could target HBMECs and deliver NGF and CUR across the blood–brain barrier. These images are consistent with the data shown in Figure 8. It has been demonstrated that modification of liposomes with anti-transferrin receptor antibody RI7217 increased the cellular uptake and showed no intracellular colocalization with early/late endosomes or early lysosomes during delivery across the blood–brain barrier.64


Rescuing apoptotic neurons in Alzheimer's disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin.

Kuo YC, Lin CC - Int J Nanomedicine (2015)

(A) Immunochemical staining images of WGA-CL-NGF-CUR-liposomes interacting with HBMECs. (a–d) CL-NGF-CUR-liposomes; (e–h) WGA-CL-NGF-CUR-liposomes; (a) rCL =0%; (b) rCL =5%; (c) rCL =10%; (d) rCL =20%; (e) CWGA =2.5 mg/mL and rCL =10%; (f) CWGA =2.5 mg/mL and rCL =20%; (g) CWGA =5 mg/mL and rCL =10%; (h) CWGA =5 mg/mL and rCL =20%. Green WGA-CL-NGF-CUR-liposomes are adjacent to red O-linked N-acetylglucosamine near blue HBMEC nuclei. (B) Fluorescent images of WGA-CL-NGF-CUR-liposomes interacting with SK-N-MC cells with an insult of Aβ1–42. (a) Control; (b–e) CL-NGF-CUR-liposomes; (b) rCL =0%; (c) rCL =5%; (d) rCL =10%; (e) rCL =20%; (f) CWGA =5 mg/mL, rCL =10%; (g) CWGA =5 mg/mL, rCL =20%. The Aβ1–42 concentration is 10 μM. Green WGA-CL-NGF-CUR-liposomes attached on red Aβ1–42, which is deposited near blue SK-N-MC cell nuclei.Abbreviations:CWGA, WGA concentration in grafting medium (mg/mL); rCL, CL mole percentage in lipids (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin; HBMECs, human brain-microvascular endothelial cells; Aβ1–42, β-amyloid1–42.
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f10-ijn-10-2653: (A) Immunochemical staining images of WGA-CL-NGF-CUR-liposomes interacting with HBMECs. (a–d) CL-NGF-CUR-liposomes; (e–h) WGA-CL-NGF-CUR-liposomes; (a) rCL =0%; (b) rCL =5%; (c) rCL =10%; (d) rCL =20%; (e) CWGA =2.5 mg/mL and rCL =10%; (f) CWGA =2.5 mg/mL and rCL =20%; (g) CWGA =5 mg/mL and rCL =10%; (h) CWGA =5 mg/mL and rCL =20%. Green WGA-CL-NGF-CUR-liposomes are adjacent to red O-linked N-acetylglucosamine near blue HBMEC nuclei. (B) Fluorescent images of WGA-CL-NGF-CUR-liposomes interacting with SK-N-MC cells with an insult of Aβ1–42. (a) Control; (b–e) CL-NGF-CUR-liposomes; (b) rCL =0%; (c) rCL =5%; (d) rCL =10%; (e) rCL =20%; (f) CWGA =5 mg/mL, rCL =10%; (g) CWGA =5 mg/mL, rCL =20%. The Aβ1–42 concentration is 10 μM. Green WGA-CL-NGF-CUR-liposomes attached on red Aβ1–42, which is deposited near blue SK-N-MC cell nuclei.Abbreviations:CWGA, WGA concentration in grafting medium (mg/mL); rCL, CL mole percentage in lipids (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin; HBMECs, human brain-microvascular endothelial cells; Aβ1–42, β-amyloid1–42.
Mentions: Figure 10A shows immunochemical staining images of binding and uptake of WGA-CL-NGF-CUR-liposomes by HBMECs via N-acetylglucosamine expressed on the cell membrane. As seen in Figure 10A(a–d), HBMECs expressed abundant N-acetylglucosamine moieties. In addition, a few CL-NGF-CUR-liposomes emerged around the HBMECs. Although the interaction between CL-NGF-CUR-liposomes and HBMECs was weak, there was some permeability of NGF across HBMEC/HA. The green intensity ratios in Figure 10Aa to d, Figure 10Ab to d, and Figure 10Ac to d were 1.18, 0.87, and 0.92, respectively. Thus, the green intensity in Figure 10Aa–d was at a similar level. As shown in Figure 10Ae–h, internalization of WGA-CL-NGF-CUR-liposomes by HBMECs was prevalent owing to the recognition of N-acetylglucosamine. Moreover, the green intensity in Figure 10Ae was 0.95 times that in Figure 10Af. Based on Figure 10Ah, the green intensity in Figure 10Ag is 0.92 times that in Figure 10Ah. Further, an increase in WGA concentration enhanced the uptake quantity, suggesting that WGA on the surface of WGA-CL-NGF-CUR-liposomes could target HBMECs and deliver NGF and CUR across the blood–brain barrier. These images are consistent with the data shown in Figure 8. It has been demonstrated that modification of liposomes with anti-transferrin receptor antibody RI7217 increased the cellular uptake and showed no intracellular colocalization with early/late endosomes or early lysosomes during delivery across the blood–brain barrier.64

Bottom Line: An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR.In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility.WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China.

ABSTRACT
Liposomes with cardiolipin (CL) and wheat germ agglutinin (WGA) were developed to permeate the blood-brain barrier and treat Alzheimer's disease. WGA-conjugated and CL-incorporated liposomes (WGA-CL-liposomes) were used to transport nerve growth factor (NGF) and curcumin (CUR) across a monolayer of human brain-microvascular endothelial cells regulated by human astrocytes and to protect SK-N-MC cells against apoptosis induced by β-amyloid1-42 (Aβ(1-42)) fibrils. An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR. In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility. WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.

No MeSH data available.


Related in: MedlinePlus