Niosomal Formulation of a Lipoyl-Carnosine Derivative Targeting TRPA1 Channels in Brain

Abstract

The transient receptor potential akyrin type-1 (TRPA1) is a non-selective cation channel playing a pivotal role in pain sensation and neurogenic inflammation. TRPA1 channels expressed in the central nervous system (CNS) have a critical role in the modulation of cortical spreading depression (CSD), which is a key pathophysiological basis of migraine pain. ADM_09 is a recently developed lipoic acid-based TRPA1 antagonist that is able to revert oxaliplatin-induced neuropathic pain and inflammatory trigeminal allodynia. In this context, aiming at developing drugs that are able to target TRPA1 channels in the CNS and promote an antioxidant effect, permeability across the blood–brain barrier (BBB) represents a central issue. Niosomes are nanovesicles that can be functionalized with specific ligands selectively recognized by transporters expressed on the BBB. In this work, the activity of ADM_09 on neocortex cultures was studied, and an efficient formulation to cross the BBB was developed with the aim of increasing the concentration of ADM_09 into the brain and selectively delivering it to the CNS rapidly after parenteral administration.

Niosomes as Biocompatible Scaffolds for the Multivalent Presentation of Tumor-Associated Antigens (TACAs) to the Immune System

“…The particle size, polydispersion index (PDI), and ζ-potential of niosomes, freshly prepared and after reconstitution, are reported in Table S1. After reconstitution, raw niosomes (blank) and niosomes- 2 have a size below 150 nm in accordance with our previous work; thus, no effect was observed on the size of niosomes loaded with glycolipid 2 . Conversely, larger vesicles were obtained upon loading with glycolipid 7 .…”

“…Niosomes were prepared using a thin-layer evaporation paddle, which was a partial modification of a previous method. , A detailed description of the niosomes’ preparation is provided in Supporting Information. The particle size, polydispersion index (PDI), and ζ-potential of niosomes, freshly prepared and after reconstitution, are reported in Table S1.…”

“…Niosomes are nanovesicles, more stable, safe, and less expensive than liposomes, obtained with synthetic surfactants that can be functionalized with precise ligands and selectively recognized by specific receptors. 24,25 The aim of this work was the preparation of niosomes decorated with multiple copies of TnThr mimetic 1 and to screen in vitro their immunogenic properties with respect to niosomes functionalized with the native TnThr antigen and to monovalent glycolipids 2 and 7 (Scheme 1).…”

“…A remarkable immunomodulatory activity was observed in in vivo trials when mimetic 1 was multivalently presented to the immune system. , Relying on the structural properties of mimetic 1 and on our previous experience regarding antigenic glycolipids assembled into vesicles, in this work we functionalized 1 with a lipid chain and the glycolipid 2 so obtained (Scheme ) was assembled into niosomes. Niosomes are nanovesicles, more stable, safe, and less expensive than liposomes, obtained with synthetic surfactants that can be functionalized with precise ligands and selectively recognized by specific receptors. , The aim of this work was the preparation of niosomes decorated with multiple copies of TnThr mimetic 1 and to screen in vitro their immunogenic properties with respect to niosomes functionalized with the native TnThr antigen and to monovalent glycolipids 2 and 7 (Scheme ).…”

Unveiling the Hidden Therapeutic Potential of Carnosine, a Molecule with a Multimodal Mechanism of Action: A Position Paper

“…By employing a rodent model of diet-induced obesity and metabolic syndrome, the authors demonstrated the ability of carnosinol to dose-dependently attenuate 4-hydroxynonenal adduct formation in liver and skeletal muscle, while simultaneously mitigating inflammation, dyslipidemia, insulin resistance, and steatohepatitis. As described by Grasso et al [ 136 ], alternative approaches to increase carnosine delivery and its bioavailability include the use of carnosine derivatives [ 137 , 138 , 139 ]; vesicular systems (nanoliposomes, niosomes, and polymerosomes) [ 140 , 141 , 142 , 143 ]; and nanoparticulate systems [ 144 , 145 , 146 , 147 ]. The currently “under-used” intranasal administration route might also represent an innovative approach, since it can purportedly bypass the BBB and first-pass metabolism [ 148 , 149 ]; the vasodilatory activity of carnosine [ 150 ] also makes this endogenous dipeptide an attractive candidate for this kind of delivery.…”