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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

Viability of HBMECs, HAs, HBVPs, and SK-N-MC cells after treatment with WGA-CL-NGF-CUR-liposomes. CWGA =5 mg/mL and rCL =20% (n=4).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; HAs, human astrocytes; HBVPs, human brain-vascular pericytes; PCV, percentage of cell viability (%).
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f7-ijn-10-2653: Viability of HBMECs, HAs, HBVPs, and SK-N-MC cells after treatment with WGA-CL-NGF-CUR-liposomes. CWGA =5 mg/mL and rCL =20% (n=4).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; HAs, human astrocytes; HBVPs, human brain-vascular pericytes; PCV, percentage of cell viability (%).

Mentions: Figure 7 shows the viability of HBMECs, HAs, HBVPs, and SK-N-MC cells. As indicated in this figure, the mean of four independent experiments using the control was defined as 100%. Thus, the presentation for the standard deviation of the control could be higher than 100%. Treatment with WGA-CL-NGF-CUR-liposomes slightly reduced the cell viability in general. This was mainly because WGA-CL-NGF-CUR-liposomes stimulated the secretion of inflammatory cytokines such as tumor necrosis factor-α.40 For bare liposomes and CL-liposomes, the viability of HBMECs, HAs, HBVPs, and SK-N-MC cells was at a comparable level. This suggests that inclusion of CL in liposomes did not jeopardize the drug delivery system. In addition, no significant difference in viability of HBMECs, HAs, HBVPs, and SK-N-MC cells was found between bare liposomes and CUR-liposomes. This suggests that the current liposomes could avoid a strong cytotoxicity induced by CUR. However, WGA on the surface slightly reduced the viability of HBMECs, HAs, HBVPs, and SK-N-MC cells. This was because the positive charge of WGA could trigger electrical intervention in the negatively charged cell systems. It has been observed that the viability of L1210 murine leukemia cells treated with liposomes containing CL for 24 hours was at the same level as the untreated control group.37 In a rodent toxicity study of liposomes containing a cationic CL analog, no rat deaths occurred after daily injection of 100 mg/kg for 3 days.41 Moreover, it has been found that modification with WGA slightly increased the toxicity of PEG-poly(lactic acid) nanoparticles in rats.29 It has been well known for decades that lipids can induce apoptosis of endothelial cells via oxidation products such as 7-oxysterols.42,43 A lipid accumulation in endothelial cells could induce apoptosis. However, the low toxicity of WGA-CL-NGF-CUR-liposomes to HBMECs, HAs, and HBVPs demonstrated a reasonable biocompatibility to normal blood–brain barrier cells. It has also been observed that anti-inflammatory capsaicin can protect against endothelial injury.44 In this study, anti-inflammatory CUR was embedded in the liposomal bilayer and improved the viability of HBMECs, HAs, and HBVPs, showing a difference between this work and a recent publication.23


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)

Viability of HBMECs, HAs, HBVPs, and SK-N-MC cells after treatment with WGA-CL-NGF-CUR-liposomes. CWGA =5 mg/mL and rCL =20% (n=4).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; HAs, human astrocytes; HBVPs, human brain-vascular pericytes; PCV, percentage of cell viability (%).
© Copyright Policy
Related In: Results  -  Collection

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

f7-ijn-10-2653: Viability of HBMECs, HAs, HBVPs, and SK-N-MC cells after treatment with WGA-CL-NGF-CUR-liposomes. CWGA =5 mg/mL and rCL =20% (n=4).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; HAs, human astrocytes; HBVPs, human brain-vascular pericytes; PCV, percentage of cell viability (%).
Mentions: Figure 7 shows the viability of HBMECs, HAs, HBVPs, and SK-N-MC cells. As indicated in this figure, the mean of four independent experiments using the control was defined as 100%. Thus, the presentation for the standard deviation of the control could be higher than 100%. Treatment with WGA-CL-NGF-CUR-liposomes slightly reduced the cell viability in general. This was mainly because WGA-CL-NGF-CUR-liposomes stimulated the secretion of inflammatory cytokines such as tumor necrosis factor-α.40 For bare liposomes and CL-liposomes, the viability of HBMECs, HAs, HBVPs, and SK-N-MC cells was at a comparable level. This suggests that inclusion of CL in liposomes did not jeopardize the drug delivery system. In addition, no significant difference in viability of HBMECs, HAs, HBVPs, and SK-N-MC cells was found between bare liposomes and CUR-liposomes. This suggests that the current liposomes could avoid a strong cytotoxicity induced by CUR. However, WGA on the surface slightly reduced the viability of HBMECs, HAs, HBVPs, and SK-N-MC cells. This was because the positive charge of WGA could trigger electrical intervention in the negatively charged cell systems. It has been observed that the viability of L1210 murine leukemia cells treated with liposomes containing CL for 24 hours was at the same level as the untreated control group.37 In a rodent toxicity study of liposomes containing a cationic CL analog, no rat deaths occurred after daily injection of 100 mg/kg for 3 days.41 Moreover, it has been found that modification with WGA slightly increased the toxicity of PEG-poly(lactic acid) nanoparticles in rats.29 It has been well known for decades that lipids can induce apoptosis of endothelial cells via oxidation products such as 7-oxysterols.42,43 A lipid accumulation in endothelial cells could induce apoptosis. However, the low toxicity of WGA-CL-NGF-CUR-liposomes to HBMECs, HAs, and HBVPs demonstrated a reasonable biocompatibility to normal blood–brain barrier cells. It has also been observed that anti-inflammatory capsaicin can protect against endothelial injury.44 In this study, anti-inflammatory CUR was embedded in the liposomal bilayer and improved the viability of HBMECs, HAs, and HBVPs, showing a difference between this work and a recent publication.23

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