ABSTRACT
We synthesized a new chalcone (4,2'-dihydroxy-3methoxy-5-bromine chalcone; C) and structurally identified it via infrared spectrometry (IR), (1)H-NMR, mass spectrometry (MS) and element analysis (EA). C was confirmed to be highly potent in scavenging 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and OH free radicals in vitro. Tests of anti-free radical activity in response to oxidative stress in mice revealed that C could elevate glutathione peroxidase (GSH-PX) and super oxide dismutase (SOD) levels and lower malonaldehyde (MDA) level in a free-radical-injured scopolamine-induced Alzheimer's model. Further behavioral tests with the Morris water maze showed that C could antagonize the learning impairments in the Alzheimer's model, which suggests that C has a potential role in Alzheimer's disease.
Subject(s)
Alzheimer Disease/metabolism , Chalcones/chemical synthesis , Chalcones/pharmacology , Disease Models, Animal , Free Radical Scavengers/pharmacology , Learning Disabilities/metabolism , Alzheimer Disease/enzymology , Animals , Glutathione Reductase/metabolism , Hepatocytes/drug effects , Hepatocytes/enzymology , L-Lactate Dehydrogenase/metabolism , Learning Disabilities/enzymology , Magnetic Resonance Spectroscopy , Malondialdehyde/metabolism , Mass Spectrometry , Maze Learning , Mice , Oxidative Stress , Spectrophotometry, Infrared , Superoxide Dismutase/metabolismABSTRACT
Star-block copolymers PEI-g-(PLL-b-PEG) with a branched polyethylenimine (PEI) core, a poly(l-lysine) (PLL) inner shell, and a poly(ethylene glycol) (PEG) outer shell have been synthesised and evaluated as potential nanocarriers for anionic drugs. The star-block copolymers were synthesised by a ring-opening polymerisation of É-benzyloxycarbonyl-L-lysine N-carboxyanhydride initiated by the peripheral primary amino groups of PEI, surface modification with activated PEG 4-nitrophenyl carbonate, and subsequent deprotection of benzyl groups on the side chains of the PLL inner shell. The synthesised star-block copolymers were characterised by (1)H NMR, gel permeation chromatography (GPC), and dynamic light scattering (DLS). The encapsulation properties of these star-block copolymers were characterised by spectrophotometric titration and dialysis. These techniques demonstrated that anionic model dyes, such as methyl orange and rose Bengal, and the model drug diclofenac sodium can be encapsulated efficiently by PEI-g-(PLL-b-PEG) at physiological pH. The entrapped model compounds demonstrated sustained release at physiological pH and accelerated release when the pH was either increased to 10.0-11.0 or decreased to 2.0-3.0. The efficient encapsulation as well as the pH-responsive releasing properties of these star-block copolymers could be potentially used in the controlled release of anionic drugs.
Subject(s)
Nanoparticles/chemistry , Pharmaceutical Preparations/chemistry , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Polylysine/chemistry , Anions/chemistry , Hydrogen-Ion ConcentrationABSTRACT
Cylindrical copolypeptide brushes PLLF-g-(PLF-b-PLG) with poly(L-lysine-co-L-phenylalanine) (PLLF) as the backbone and poly(L-phenylalanine)-b-poly(L-glutamic acid) (PLF-b-PLG) as the side chains have been synthesized and evaluated as drug delivery carriers. The synthesized copolypeptide brushes were characterized by (1)H NMR, gel permeation chromatography (GPC), and transmission electron microscopy (TEM). In aqueous solution, the copolypeptide brushes adopt cylindrical morphologies and resemble unimolecular polymeric micelles with a hydrophobic poly(L-phenylalanine) core and a hydrophilic poly(L-glutamate) shell. An encapsulation study demonstrated that these water soluble, biodegradable copolypeptide brushes encapsulate hydrophobic compounds and cationic hydrophilic guest molecules simultaneously. Furthermore, the encapsulated cationic model compounds exhibit a pH-responsive releasing property.
Subject(s)
Drug Carriers/chemical synthesis , Peptides/chemical synthesis , Surface-Active Agents/chemical synthesis , Anions , Cations , Chromatography, Gel , Drug Compounding , Hydrophobic and Hydrophilic Interactions , Magnetic Resonance Spectroscopy , Micelles , Microscopy, Electron, Transmission , Nanostructures/chemistry , Nanostructures/ultrastructure , Prescription Drugs/chemistry , SolutionsABSTRACT
A hydrophilic star block co-polymer was synthesized, characterized, and evaluated as a protein nanocarrier. The star block co-polymer was composed of a hyperbranched polyethylenimine (PEI) core, a poly(L-lysine) (PLL) inner shell, and a poly(ethylene glycol) (PEG) outer shell. The model protein insulin can be rapidly and efficiently encapsulated by the synthesized polymer in aqueous phosphate buffer at physiological pH. Complexation between PEI-PLL-b-PEG and insulin was investigated using native polyacrylamide gel electrophoresis. The uptake of enhanced green fluorescent protein into Ad293 cells mediated by PEI-PLL-b-PEG was also investigated. The encapsulated insulin demonstrated sustained release at physiological pH and showed accelerated release when the pH was decreased. The insulin released from the star block co-polymer retained its chemical integrity and immunogenicity.
Subject(s)
Drug Carriers , Hydrogen-Ion Concentration , Polylysine/chemistry , Polymers/chemistry , Proteins/administration & dosage , Chromatography, High Pressure Liquid , Electrophoresis, Polyacrylamide Gel , Insulin/administration & dosage , Magnetic Resonance Spectroscopy , Spectroscopy, Fourier Transform InfraredABSTRACT
The synthesis of water soluble star-block copolypeptides and their encapsulation properties are described. The star-block copolypeptides, obtained by ring-opening polymerization of amino acid N-carboxyanhydrides, consist of a PEI core, a hydrophobic polyphenylalanine or polyleucine inner shell, and a negatively charged polyglutamate outer shell. The encapsulation study showed that these water soluble, amphiphilic star-block copolypeptides could simultaneously encapsulate versatile compounds ranging from hydrophobic to anionic and cationic hydrophilic guest molecules.
