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

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-amyloid 1–42 (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.

Effects of Micro-environmental pH of Liposome on Chemical Stability of Loaded Drug

“…As shown in Table 1, all these profiles showed very good linearity with fitting degree higher than 0.99 (regression equations are also displayed), suggesting that the release of Cur-LPs fitted to zero-order kinetics. In other similar studies, the release of curcumin from liposome was found to be non-linear [38,39]. From the point view of drug research and development, zero-order release kinetics is the most ideal release profile because it provides a constant drug release rate and thus is able to maintain therapeutic effect for a long time, decrease administration times, and reduce side effects.…”

Vinorelbine cationic liposomes modified with wheat germ agglutinin for inhibiting tumor metastasis in treatment of brain glioma

“…WGA could binds to N-acetyl-D-glucosamine and sialic acid with low toxicity to the normal tissues [15]. It was reported that WGA could enhance the transport ability across the BBB by receptor-mediated endocytosis [16], and the modification of WGA on nanoparticles could potentiate the targeting effects to tumor cells by the specifically binding to glycoproteins overexpressed on cytomembrane [17]. As one of the most useful strategies, cationic liposomes have been used as excellent delivery carriers for their targeting property to tumor cells or tumor vascular cells by electrostatic interaction [18].…”

Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer’s disease treatment

“…29 Furthermore, exogenous NGF is regarded as an important bioactive element with inadequate bioavailability in the brain because it is hydrophilic and bulky with a molecular weight of 27 kDa. 30 The current LIP carriers with WGA and CL could be practical formulations to enhance the usability of CRM and NGF in the brain. As shown in Figure 1F, the order in the cytotoxicity was CRM ≅ WGA-CRM-CL/LIP .…”