Rescuing apoptotic neurons in Alzheimer's disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin

• Published in: International journal of nanomedicine 2015-04, Vol.10 (default), p.2653-2672
• Main Authors: Kuo, Yung-Chih, Lin, Ching-Chun
• Format: Article
• Language: English
• Subjects: Alzheimer Disease; Alzheimer's disease; Apoptosis - drug effects; Bioavailability; Brain research; Cardiolipin; Cardiolipins - chemistry; Cardiolipins - pharmacology; Care and treatment; curcumin; Curcumin - chemistry; Curcumin - pharmacology; Diagnosis; Growth factors; Humans; Lipids; liposome; Liposomes; Liposomes - chemistry; Liposomes - pharmacology; Metabolism; Nerve growth factor; Nerve Growth Factor - chemistry; Nerve Growth Factor - pharmacology; Nervous system; Neuroblastoma; Neurons - drug effects; Original Research; Peptides; Permeability; Physiological aspects; Polyethylene glycol; Polyethylene terephthalate; Pore size; Proteins; Triticum aestivum; wheat germ agglutinin; Wheat Germ Agglutinins - chemistry; Wheat Germ Agglutinins - pharmacology
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S79528

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.