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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

Dissolution profile for NGF (A) and CUR (B) from WGA-CL-NGF-CUR-liposomes. (⋄) rCL =0%; (□) rCL =5%; (○) rCL =10%; (△) rCL =20%. CWGA =5 mg/mL (n=3).Abbreviations:CWGA, WGA concentration in grafting medium (mg/mL); rCL, CL mole percentage in lipids (%); PCUR, accumulated percentage of CUR released from WGA-CL-NGF-CUR-liposomes (%); PNGF, accumulated percentage of NGF released from WGA-CL-NGF-CUR-liposomes (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
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f6-ijn-10-2653: Dissolution profile for NGF (A) and CUR (B) from WGA-CL-NGF-CUR-liposomes. (⋄) rCL =0%; (□) rCL =5%; (○) rCL =10%; (△) rCL =20%. CWGA =5 mg/mL (n=3).Abbreviations:CWGA, WGA concentration in grafting medium (mg/mL); rCL, CL mole percentage in lipids (%); PCUR, accumulated percentage of CUR released from WGA-CL-NGF-CUR-liposomes (%); PNGF, accumulated percentage of NGF released from WGA-CL-NGF-CUR-liposomes (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.

Mentions: Figure 6 shows the dissolution kinetics of NGF and CUR from WGA-CL-NGF-CUR-liposomes. As indicated in this figure, no initial burst of NGF and CUR was obtained. The molecular weight of human β-NGF is about 27 kDa.38 The NGF liberated from WGA-CL-NGF-CUR-liposomes could permeate a cellulose membrane of 50 kDa. The accumulated percentage of NGF released from WGA-CL-NGF-CUR-liposomes over 6 hours was about 20%–32%, which was lower than the corresponding CUR release percentage of 35%–55%. In addition, the release rate decelerated over 48 hours. The accumulated percentage of NGF released from WGA-CL-NGF-CUR-liposomes over 48 hours was about 50%–72%, which is comparable with the 55%–75% for CUR. In this stage, the dissolution behavior resulted from collision between WGA-CL-NGF-CUR-liposomes and migration of NGF through the membrane or detachment of CUR from the liposomal bilayer. As indicated in Figure 6A, an increase in the CL mole percentage accelerated the release of NGF from the WGA-CL-NGF-CUR-liposomes. This acceleration was because the high level of CL reduced the cholesterol content available for lipid assembly, decreased the tightness and closure of the sealed configuration in the WGA-CL-NGF-CUR-liposomes, and enhanced the fluidity of the liposomal bilayer. It has been suggested that cholesterol with its particular planar ring structure is an important component of the cell membrane and can generate a compact configuration in the bilayer via hydrogen bonding between its hydroxyl group and the head groups of phospholipids.39 As indicated in Figure 6B, an increase in the CL mole percentage slowed the release of CUR from the WGA-CL-NGF-CUR-liposomes. Two reasons could explain this deceleration. First, the affinity of CUR for CL was stronger than that for other phospholipids. Second, an increase in the CL mole percentage increased the absolute zeta potential (data shown in Table 1), decreased the possibility of liposomal collision, and reduced the deterioration of the bilayer structure where CUR was entrapped.


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)

Dissolution profile for NGF (A) and CUR (B) from WGA-CL-NGF-CUR-liposomes. (⋄) rCL =0%; (□) rCL =5%; (○) rCL =10%; (△) rCL =20%. CWGA =5 mg/mL (n=3).Abbreviations:CWGA, WGA concentration in grafting medium (mg/mL); rCL, CL mole percentage in lipids (%); PCUR, accumulated percentage of CUR released from WGA-CL-NGF-CUR-liposomes (%); PNGF, accumulated percentage of NGF released from WGA-CL-NGF-CUR-liposomes (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
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f6-ijn-10-2653: Dissolution profile for NGF (A) and CUR (B) from WGA-CL-NGF-CUR-liposomes. (⋄) rCL =0%; (□) rCL =5%; (○) rCL =10%; (△) rCL =20%. CWGA =5 mg/mL (n=3).Abbreviations:CWGA, WGA concentration in grafting medium (mg/mL); rCL, CL mole percentage in lipids (%); PCUR, accumulated percentage of CUR released from WGA-CL-NGF-CUR-liposomes (%); PNGF, accumulated percentage of NGF released from WGA-CL-NGF-CUR-liposomes (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor; WGA, wheat germ agglutinin.
Mentions: Figure 6 shows the dissolution kinetics of NGF and CUR from WGA-CL-NGF-CUR-liposomes. As indicated in this figure, no initial burst of NGF and CUR was obtained. The molecular weight of human β-NGF is about 27 kDa.38 The NGF liberated from WGA-CL-NGF-CUR-liposomes could permeate a cellulose membrane of 50 kDa. The accumulated percentage of NGF released from WGA-CL-NGF-CUR-liposomes over 6 hours was about 20%–32%, which was lower than the corresponding CUR release percentage of 35%–55%. In addition, the release rate decelerated over 48 hours. The accumulated percentage of NGF released from WGA-CL-NGF-CUR-liposomes over 48 hours was about 50%–72%, which is comparable with the 55%–75% for CUR. In this stage, the dissolution behavior resulted from collision between WGA-CL-NGF-CUR-liposomes and migration of NGF through the membrane or detachment of CUR from the liposomal bilayer. As indicated in Figure 6A, an increase in the CL mole percentage accelerated the release of NGF from the WGA-CL-NGF-CUR-liposomes. This acceleration was because the high level of CL reduced the cholesterol content available for lipid assembly, decreased the tightness and closure of the sealed configuration in the WGA-CL-NGF-CUR-liposomes, and enhanced the fluidity of the liposomal bilayer. It has been suggested that cholesterol with its particular planar ring structure is an important component of the cell membrane and can generate a compact configuration in the bilayer via hydrogen bonding between its hydroxyl group and the head groups of phospholipids.39 As indicated in Figure 6B, an increase in the CL mole percentage slowed the release of CUR from the WGA-CL-NGF-CUR-liposomes. Two reasons could explain this deceleration. First, the affinity of CUR for CL was stronger than that for other phospholipids. Second, an increase in the CL mole percentage increased the absolute zeta potential (data shown in Table 1), decreased the possibility of liposomal collision, and reduced the deterioration of the bilayer structure where CUR was entrapped.

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