Bi-functional sterically hindered phenol lipid-based delivery systems as potential multi-target agents against Alzheimer's disease via an intranasal route

Abstract

<p>New lipid-based nanomaterials based on sterically hindered phenols were developed as potential drugs against Alzheimer's disease <italic>via</italic> intranasal administration.</p>

Slow-binding reversible inhibitor of acetylcholinesterase with long-lasting action for prophylaxis of organophosphate poisoning

“…Also, the nanotechnological approach as a strategy for delivery of C457 or similar compounds into the brain is appealing. In the last few years, nanoparticles have been successfully used for delivery of either quaternized oximes or AChE reversible charged inhibitors into the brain 55 – 57 . Thus, nano-cargos could be implemented to overcome the problem of the blood–brain barrier penetration for AChE inhibitors with long-lasting action as potential drugs for prolonged pre‐exposure treatment of OP-induced neurodegeneration.…”

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

“…Research activity of our group focuses on self-assembling amphiphilic systems, with their design, aggregation ability and functionality as drug delivery systems emphasized [2,37,38]. Recently, much attention has been paid to non-covalent modification of liposomes with surfactants [37][38][39][40], with cationic liposomes attracting special interest [41][42][43][44][45][46][47]. Main types of lipid-and silicon-containing nanoparticles, comprising many kinds of nanocarriers that can be used to achieve the best medical performance.…”

“…Research activity of our group focuses on self-assembling amphiphilic systems, with their design, aggregation ability and functionality as drug delivery systems emphasized [2,37,38]. Recently, much attention has been paid to non-covalent modification of liposomes with surfactants [37][38][39][40], with cationic liposomes attracting special interest [41][42][43][44][45][46][47]. In [39,40] lipid nanoformulations based on L-α-phosphatidylcholine (PC), cholesterol (CHO) and hybrid amphiphilic ligands-quaternary ammonium salts with a sterically hindered phenolic (SHP) moiety with benzyl (SHP-2-Bn) and alkyl tails (SHP-2-R, where R=C n H 2n+1 , n = 8, 10, 12, 16) were obtained and characterized.…”

“…Recently, much attention has been paid to non-covalent modification of liposomes with surfactants [37][38][39][40], with cationic liposomes attracting special interest [41][42][43][44][45][46][47]. In [39,40] lipid nanoformulations based on L-α-phosphatidylcholine (PC), cholesterol (CHO) and hybrid amphiphilic ligands-quaternary ammonium salts with a sterically hindered phenolic (SHP) moiety with benzyl (SHP-2-Bn) and alkyl tails (SHP-2-R, where R=C n H 2n+1 , n = 8, 10, 12, 16) were obtained and characterized. Cationic liposomes based on PC with a diameter of 100 nm, modified with benzyl derivatives of SHP, exhibit more pronounced antioxidant activity than individual SHP-n-Bn.…”

“…Alkyl-conjugated SHPs exhibit inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase in combination with antioxidant properties, which allowed them to be considered as candidates for drugs against Alzheimer's disease. Based on the data on self-assembly, their lipophilicity has been optimized and the relationship between biological activity and toxicity has been evaluated, which served as fundamentals for the development of multitargeted liposomal formulations [40]. Intranasal (in vivo) administration of PC/SHP-2-Bn/SHP-2-16 liposomes to rats (dose SHP-2-16 8 mg/kg) showed their ability to overcome the blood-brain barrier (BBB), providing the inhibition of AChE in the brain (up to 15.46%) (Figure 2).…”