Limits...
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

Permeability of NGF (A) and CUR (B) across HBMEC/HA using WGA-CL-NGF-CUR-liposomes. (b–e) Black bar, CL-NGF-CUR-liposomes; gray bar, WGA-CL-NGF-CUR-liposomes, CWGA =5 mg/mL. (b) rCL =0%; (c) rCL =5%; (d) rCL =10%; (e) rCL =20%. (A): (a) free NGF; (b)-(e) CL-NGF-liposome; (B): (a) free CUR; (b–e) CL-CUR-liposome (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; HBMEC, human brain-microvascular endothelial cell; HA, human astrocyte.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4388084&req=5

f8-ijn-10-2653: Permeability of NGF (A) and CUR (B) across HBMEC/HA using WGA-CL-NGF-CUR-liposomes. (b–e) Black bar, CL-NGF-CUR-liposomes; gray bar, WGA-CL-NGF-CUR-liposomes, CWGA =5 mg/mL. (b) rCL =0%; (c) rCL =5%; (d) rCL =10%; (e) rCL =20%. (A): (a) free NGF; (b)-(e) CL-NGF-liposome; (B): (a) free CUR; (b–e) CL-CUR-liposome (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; HBMEC, human brain-microvascular endothelial cell; HA, human astrocyte.

Mentions: Figure 8 shows the permeability of NGF and CUR across HBMEC/HA. In this study, the TEER of HBMEC/HA treated with liposomal carriers varied from 191 Ω × cm2 to 233 Ω × cm2, demonstrating satisfactory tightness for investigating delivery across the blood–brain barrier. The control TEER value (no treatment with nanocarriers) was 243±4 Ω × cm2 (n=4). The control PI permeability coefficient across HBMEC/HA was (3.8±0.3) ×10−6 cm/sec (n=4), defining a compact monolayer with a high level of tight junctions that does not allow small molecules to pass by paracellular transport. As indicated in Figure 8A, CL-NGF-liposomes (indicated by black bars in Figure 8Ab–e) enhanced the permeability for NGF when compared with free NGF (Figure 8Aa). Modification with WGA markedly increased the permeability for NGF. As shown in Figure 8B, CL-CUR-liposomes reduced the permeability for CUR when compared with free CUR. Conjugation of WGA on the surface of WGA-CL-CUR-liposomes enhanced the permeability of CUR. However, an increase in the CL mole percentage did not significantly change the permeability of NGF and CUR. There are five possible reasons for these results. First, free hydrophilic NGF with a molecular weight of about 27 kDa was not able to infiltrate HBMEC/HA. The slight penetration of NGF across HBMEC/HA resulted from its affinity for neurotrophic tyrosine kinase receptor type 1 expressed on HBMECs.45 Second, free hydrophobic CUR with a molecular weight of 368 Da infiltrates HBMEC/HA easily. It has been shown that hydrophobic drugs with a molecular weight smaller than 400 Da are likely to permeate the blood–brain barrier.46 Third, the bilayer structure and phospholipid composition of CL-NGF-liposomes is similar to that of cell membranes. Therefore, the membrane fusion of CL-NGF-liposomes with HBMECs enabled permeation of NGF across HBMEC/HA. However, CL-CUR-liposomes physically hindered the ability of CUR to traverse the blood–brain barrier. Although CL-CUR-liposomes reduced the permeability of CUR across the blood–brain barrier, they could reduce the toxicity of CUR and enhance its bioavailability. Fourth, positively charged WGA could preferentially interact with the negatively charged HBMECs via electrostatic attraction and activate adsorptive-mediated transcytosis.47 In addition, HBMECs carry N-acetylglucosamine, which is recognized by surface WGA.22 It has also been demonstrated that WGA has a high affinity for porcine capillary endothelial cells and has low toxicity.48 Fifth, HBMECs did not carry ligands for conjugating CL. However, it has been observed that CL is widely distributed in the inner membranes of liver mitochondria for specific molecular regulation.49 In a study of the permeation characteristics of calcium, CL-enriched liposomes were shown to decrease calcium uptake, as estimated by cytochrome oxidase vesicles.50


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)

Permeability of NGF (A) and CUR (B) across HBMEC/HA using WGA-CL-NGF-CUR-liposomes. (b–e) Black bar, CL-NGF-CUR-liposomes; gray bar, WGA-CL-NGF-CUR-liposomes, CWGA =5 mg/mL. (b) rCL =0%; (c) rCL =5%; (d) rCL =10%; (e) rCL =20%. (A): (a) free NGF; (b)-(e) CL-NGF-liposome; (B): (a) free CUR; (b–e) CL-CUR-liposome (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; HBMEC, human brain-microvascular endothelial cell; HA, human astrocyte.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-2653: Permeability of NGF (A) and CUR (B) across HBMEC/HA using WGA-CL-NGF-CUR-liposomes. (b–e) Black bar, CL-NGF-CUR-liposomes; gray bar, WGA-CL-NGF-CUR-liposomes, CWGA =5 mg/mL. (b) rCL =0%; (c) rCL =5%; (d) rCL =10%; (e) rCL =20%. (A): (a) free NGF; (b)-(e) CL-NGF-liposome; (B): (a) free CUR; (b–e) CL-CUR-liposome (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; HBMEC, human brain-microvascular endothelial cell; HA, human astrocyte.
Mentions: Figure 8 shows the permeability of NGF and CUR across HBMEC/HA. In this study, the TEER of HBMEC/HA treated with liposomal carriers varied from 191 Ω × cm2 to 233 Ω × cm2, demonstrating satisfactory tightness for investigating delivery across the blood–brain barrier. The control TEER value (no treatment with nanocarriers) was 243±4 Ω × cm2 (n=4). The control PI permeability coefficient across HBMEC/HA was (3.8±0.3) ×10−6 cm/sec (n=4), defining a compact monolayer with a high level of tight junctions that does not allow small molecules to pass by paracellular transport. As indicated in Figure 8A, CL-NGF-liposomes (indicated by black bars in Figure 8Ab–e) enhanced the permeability for NGF when compared with free NGF (Figure 8Aa). Modification with WGA markedly increased the permeability for NGF. As shown in Figure 8B, CL-CUR-liposomes reduced the permeability for CUR when compared with free CUR. Conjugation of WGA on the surface of WGA-CL-CUR-liposomes enhanced the permeability of CUR. However, an increase in the CL mole percentage did not significantly change the permeability of NGF and CUR. There are five possible reasons for these results. First, free hydrophilic NGF with a molecular weight of about 27 kDa was not able to infiltrate HBMEC/HA. The slight penetration of NGF across HBMEC/HA resulted from its affinity for neurotrophic tyrosine kinase receptor type 1 expressed on HBMECs.45 Second, free hydrophobic CUR with a molecular weight of 368 Da infiltrates HBMEC/HA easily. It has been shown that hydrophobic drugs with a molecular weight smaller than 400 Da are likely to permeate the blood–brain barrier.46 Third, the bilayer structure and phospholipid composition of CL-NGF-liposomes is similar to that of cell membranes. Therefore, the membrane fusion of CL-NGF-liposomes with HBMECs enabled permeation of NGF across HBMEC/HA. However, CL-CUR-liposomes physically hindered the ability of CUR to traverse the blood–brain barrier. Although CL-CUR-liposomes reduced the permeability of CUR across the blood–brain barrier, they could reduce the toxicity of CUR and enhance its bioavailability. Fourth, positively charged WGA could preferentially interact with the negatively charged HBMECs via electrostatic attraction and activate adsorptive-mediated transcytosis.47 In addition, HBMECs carry N-acetylglucosamine, which is recognized by surface WGA.22 It has also been demonstrated that WGA has a high affinity for porcine capillary endothelial cells and has low toxicity.48 Fifth, HBMECs did not carry ligands for conjugating CL. However, it has been observed that CL is widely distributed in the inner membranes of liver mitochondria for specific molecular regulation.49 In a study of the permeation characteristics of calcium, CL-enriched liposomes were shown to decrease calcium uptake, as estimated by cytochrome oxidase vesicles.50

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