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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

X-ray photoelectron spectra of WGA-CL-NGF-CUR-liposomes. The inlet graphs on each spectrum are the magnified nitrogen signals.Notes: (A) CWGA =2.5 mg/mL and rCL =10%; (B) CWGA =2.5 mg/mL and rCL =20%; (C) CWGA =5 mg/mL and rCL =10%; (D) CWGA =5 mg/mL and rCL =20%.Abbreviations:rCL, CL mole percentage in lipids (%); CWGA, WGA concentration in grafting medium (mg/mL); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
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f4-ijn-10-2653: X-ray photoelectron spectra of WGA-CL-NGF-CUR-liposomes. The inlet graphs on each spectrum are the magnified nitrogen signals.Notes: (A) CWGA =2.5 mg/mL and rCL =10%; (B) CWGA =2.5 mg/mL and rCL =20%; (C) CWGA =5 mg/mL and rCL =10%; (D) CWGA =5 mg/mL and rCL =20%.Abbreviations:rCL, CL mole percentage in lipids (%); CWGA, WGA concentration in grafting medium (mg/mL); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.

Mentions: Figure 4 shows the XPS spectra for the WGA-CL-NGF-CUR-liposomes. The peaks at 132 eV, 282 eV, 401 eV, and 532 eV belonged to the signals of phosphorus, carbon, nitrogen, and oxygen, respectively, on the surface of WGA-CL-NGF-CUR-liposomes. As indicated in Figure 4, the phosphorus intensity was roughly a constant, when the CL mole percentage increased from 10% to 20% and the WGA concentration increased from 2.5 mg/mL to 5 mg/mL. However, the nitrogen intensity fluctuated, when the CL mole percentage and WGA concentration varied. Table 2 shows the effect of the CL mole percentage and WGA concentration on the atomic ratio of nitrogen to phosphorus. As seen in this table, an increase in the CL mole percentage reduced the atomic percentage of nitrogen. This was because CL contains phosphorus but does not bear nitrogen. In addition, an increase in the WGA concentration increased the atomic ratio of nitrogen to phosphorus. This was because WGA carries ample nitrogen atoms. Table 2 also shows the grafting efficiency of WGA on WGA-CL-NGF-CUR-liposomes. This table further shows that an increase in the CL mole percentage enhanced the grafting efficiency. This was mainly because the negatively charged CL in the liposomal bilayer could attract positively charged WGA to the vicinity of WGA-CL-NGF-CUR-liposomes via electrical interaction. Based on the WGA grafting efficiency, an increase in the CL mole percentage could increase the quantity of nitrogen in the WGA-CL-NGF-CUR-liposomes. However, based on the atomic ratio of nitrogen to phosphorus, an increase in the CL mole percentage reduced the overall nitrogen quantity on the WGA-CL-NGF-CUR-liposomes. Moreover, an increase in the WGA concentration decreased the grafting efficiency. This was because a high level of WGA increased the competition among WGA molecules for surface carboxyl groups. In fact, the self-competition to occupy the nanoparticle surface was intensified by the more active molecules involved, such as WGA and transferrin.32 It has been observed that the hydrophilic Beclin 1 evolutionarily conserved domain could be preferably conjugated on a lipid membrane enriched with CL.33 This was due to small head groups and large hydrophobic tails in the molecular structure of CL.


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)

X-ray photoelectron spectra of WGA-CL-NGF-CUR-liposomes. The inlet graphs on each spectrum are the magnified nitrogen signals.Notes: (A) CWGA =2.5 mg/mL and rCL =10%; (B) CWGA =2.5 mg/mL and rCL =20%; (C) CWGA =5 mg/mL and rCL =10%; (D) CWGA =5 mg/mL and rCL =20%.Abbreviations:rCL, CL mole percentage in lipids (%); CWGA, WGA concentration in grafting medium (mg/mL); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
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f4-ijn-10-2653: X-ray photoelectron spectra of WGA-CL-NGF-CUR-liposomes. The inlet graphs on each spectrum are the magnified nitrogen signals.Notes: (A) CWGA =2.5 mg/mL and rCL =10%; (B) CWGA =2.5 mg/mL and rCL =20%; (C) CWGA =5 mg/mL and rCL =10%; (D) CWGA =5 mg/mL and rCL =20%.Abbreviations:rCL, CL mole percentage in lipids (%); CWGA, WGA concentration in grafting medium (mg/mL); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
Mentions: Figure 4 shows the XPS spectra for the WGA-CL-NGF-CUR-liposomes. The peaks at 132 eV, 282 eV, 401 eV, and 532 eV belonged to the signals of phosphorus, carbon, nitrogen, and oxygen, respectively, on the surface of WGA-CL-NGF-CUR-liposomes. As indicated in Figure 4, the phosphorus intensity was roughly a constant, when the CL mole percentage increased from 10% to 20% and the WGA concentration increased from 2.5 mg/mL to 5 mg/mL. However, the nitrogen intensity fluctuated, when the CL mole percentage and WGA concentration varied. Table 2 shows the effect of the CL mole percentage and WGA concentration on the atomic ratio of nitrogen to phosphorus. As seen in this table, an increase in the CL mole percentage reduced the atomic percentage of nitrogen. This was because CL contains phosphorus but does not bear nitrogen. In addition, an increase in the WGA concentration increased the atomic ratio of nitrogen to phosphorus. This was because WGA carries ample nitrogen atoms. Table 2 also shows the grafting efficiency of WGA on WGA-CL-NGF-CUR-liposomes. This table further shows that an increase in the CL mole percentage enhanced the grafting efficiency. This was mainly because the negatively charged CL in the liposomal bilayer could attract positively charged WGA to the vicinity of WGA-CL-NGF-CUR-liposomes via electrical interaction. Based on the WGA grafting efficiency, an increase in the CL mole percentage could increase the quantity of nitrogen in the WGA-CL-NGF-CUR-liposomes. However, based on the atomic ratio of nitrogen to phosphorus, an increase in the CL mole percentage reduced the overall nitrogen quantity on the WGA-CL-NGF-CUR-liposomes. Moreover, an increase in the WGA concentration decreased the grafting efficiency. This was because a high level of WGA increased the competition among WGA molecules for surface carboxyl groups. In fact, the self-competition to occupy the nanoparticle surface was intensified by the more active molecules involved, such as WGA and transferrin.32 It has been observed that the hydrophilic Beclin 1 evolutionarily conserved domain could be preferably conjugated on a lipid membrane enriched with CL.33 This was due to small head groups and large hydrophobic tails in the molecular structure of CL.

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