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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

Effect of CL mole percentage on NGF entrapment efficiency (A) and CUR entrapment efficiency (B) in CL-NGF-CUR-liposomes. (A): (○) CL-NGF-liposome; (□) CL-NGF-CUR-liposome. (B): (○) CL-CUR-liposome; (□) CL-NGF-CUR-liposome (n=3).Abbreviations:rCL, CL mole percentage in lipids (%); ECUR, CUR entrapment efficiency in CL-NGF-CUR-liposomes (%); ENGF, NGF entrapment efficiency in CL-NGF-CUR-liposomes (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor.
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f5-ijn-10-2653: Effect of CL mole percentage on NGF entrapment efficiency (A) and CUR entrapment efficiency (B) in CL-NGF-CUR-liposomes. (A): (○) CL-NGF-liposome; (□) CL-NGF-CUR-liposome. (B): (○) CL-CUR-liposome; (□) CL-NGF-CUR-liposome (n=3).Abbreviations:rCL, CL mole percentage in lipids (%); ECUR, CUR entrapment efficiency in CL-NGF-CUR-liposomes (%); ENGF, NGF entrapment efficiency in CL-NGF-CUR-liposomes (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor.

Mentions: Figure 5 shows the entrapment efficiency of NGF and CUR in the CL-NGF-CUR-liposomes. As indicated in Figure 5A, an increase in the CL mole percentage enhanced the entrapment efficiency of NGF. This was because negatively charged CL could attract cationic NGF to the aqueous interior. In addition, incorporation of CUR reduced the entrapment efficiency of NGF. This was because the interaction between CUR and the membrane lipids might extend the bilayer region and shrink the core space in the CL-NGF-CUR-liposomes. As shown in Figure 5B, an increase in the CL mole percentage enhanced the entrapment efficiency of CUR. This could be explained as follows. First, a CL molecule contains four hydrophobic tails and has a strong affinity for hydrophobic CUR. Second, an equal mole percentage of DPPC and cholesterol was used in every batch of lipid mixture. An increase in the CL mole percentage decreased the cholesterol fraction in the liposome formulation, leading to a decrease in the rigidity of the lipid bilayer of the liposomes and less entrapment efficiency of the CUR bilayer inside. Moreover, incorporation of NGF enhanced the entrapment efficiency of CUR. This was because positively charged NGF emerged uniformly near the inner bilayer, leading to a uniform distribution of negatively charged phospholipids in the CL-NGF-CUR-liposomes and accelerating the CUR encapsulation rate. It has been observed that addition of phosphatidylcholine to lipids increases the entrapment of CUR in the phospholipid bilayer.34 In fact, soybean phospholipids, egg yolk phospholipids, and hydrogenated soybean phospholipids could be effective in encapsulating CUR.35 It has also been found that CUR could be accommodated in liposomal cores via its high solubility in 2-hydroxypropyl-γ-cyclodextrin.36 Further, CL in anionic liposomes could benefit an encapsulation of cationic drug.37


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)

Effect of CL mole percentage on NGF entrapment efficiency (A) and CUR entrapment efficiency (B) in CL-NGF-CUR-liposomes. (A): (○) CL-NGF-liposome; (□) CL-NGF-CUR-liposome. (B): (○) CL-CUR-liposome; (□) CL-NGF-CUR-liposome (n=3).Abbreviations:rCL, CL mole percentage in lipids (%); ECUR, CUR entrapment efficiency in CL-NGF-CUR-liposomes (%); ENGF, NGF entrapment efficiency in CL-NGF-CUR-liposomes (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388084&req=5

f5-ijn-10-2653: Effect of CL mole percentage on NGF entrapment efficiency (A) and CUR entrapment efficiency (B) in CL-NGF-CUR-liposomes. (A): (○) CL-NGF-liposome; (□) CL-NGF-CUR-liposome. (B): (○) CL-CUR-liposome; (□) CL-NGF-CUR-liposome (n=3).Abbreviations:rCL, CL mole percentage in lipids (%); ECUR, CUR entrapment efficiency in CL-NGF-CUR-liposomes (%); ENGF, NGF entrapment efficiency in CL-NGF-CUR-liposomes (%); CL, cardiolipin; CUR, curcumin; NGF, nerve growth factor.
Mentions: Figure 5 shows the entrapment efficiency of NGF and CUR in the CL-NGF-CUR-liposomes. As indicated in Figure 5A, an increase in the CL mole percentage enhanced the entrapment efficiency of NGF. This was because negatively charged CL could attract cationic NGF to the aqueous interior. In addition, incorporation of CUR reduced the entrapment efficiency of NGF. This was because the interaction between CUR and the membrane lipids might extend the bilayer region and shrink the core space in the CL-NGF-CUR-liposomes. As shown in Figure 5B, an increase in the CL mole percentage enhanced the entrapment efficiency of CUR. This could be explained as follows. First, a CL molecule contains four hydrophobic tails and has a strong affinity for hydrophobic CUR. Second, an equal mole percentage of DPPC and cholesterol was used in every batch of lipid mixture. An increase in the CL mole percentage decreased the cholesterol fraction in the liposome formulation, leading to a decrease in the rigidity of the lipid bilayer of the liposomes and less entrapment efficiency of the CUR bilayer inside. Moreover, incorporation of NGF enhanced the entrapment efficiency of CUR. This was because positively charged NGF emerged uniformly near the inner bilayer, leading to a uniform distribution of negatively charged phospholipids in the CL-NGF-CUR-liposomes and accelerating the CUR encapsulation rate. It has been observed that addition of phosphatidylcholine to lipids increases the entrapment of CUR in the phospholipid bilayer.34 In fact, soybean phospholipids, egg yolk phospholipids, and hydrogenated soybean phospholipids could be effective in encapsulating CUR.35 It has also been found that CUR could be accommodated in liposomal cores via its high solubility in 2-hydroxypropyl-γ-cyclodextrin.36 Further, CL in anionic liposomes could benefit an encapsulation of cationic drug.37

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