calixarenes and Hemolysis

Topics: Biofilms; Calixarenes; Cell Line, Tumor; Hemolysis; Humans; Microbial Sensitivity Tests; Polyelectrolytes; Pseudomonas aeruginosa; Quaternary Ammonium Compounds; Rotaxanes

Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor.. Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model.. Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo.. In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.

Topics: Acetylcholinesterase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Calixarenes; Cell Survival; Chemical and Drug Induced Liver Injury; Cholinesterase Inhibitors; Drug Carriers; Drug Liberation; Fluorescein; Hemolysis; Liver; Male; Mice, Inbred C57BL; Nanoparticles; Phenols; Porosity; Rats; Silicon Dioxide; Temperature; Time Factors

Five unimolecular channels with different lengths are presented. The varying length of these channels has significant impact on their transmembrane transport properties, which are directly correlated with their antimicrobial activity and inversely correlated with their haemolytic toxicity. By further structural optimization, these new channels could reach high antimicrobial activity and very low haemolytic toxicity, with the potential to serve as systemic antibiotics.

Topics: Anti-Infective Agents; Biological Transport; Calixarenes; Hemolysis; Ion Channels; Macrocyclic Compounds; Models, Molecular; Molecular Structure; Peptides; Quaternary Ammonium Compounds

A series of products based on tert-butylcalix[4]arene have been synthesized by anionic polymerization of ethylene oxide. The resulting products are amphiphilic octopus-shaped macromolecules, consisting of a hydrophobic calix[4]arene core and four arms of hydrophilic poly(ethylene oxide) chains. In aqueous solutions the polyoxyethylated tert-butylcalix[4]arenes were found to self-associate above certain CMC determined by dye solubilization technique. The light scattering study reveals that the polyoxyethylated tert-butylcalix[4]arenes form aggregates of narrow size distribution and hydrodynamic diameters ranging from about 155 to 245 nm and aggregation numbers from tens to hundreds macromolecules per particle depending on the degree of polymerization of the PEO chains. An in vitro biocompatibility study showed that the tested compounds are practically devoid of intrinsic cytotoxic and hemolytic effects and moreover they failed to modulate the mitogen-induced interleukin-2 release from the human T-lymphocyte cell line Jurkat E6-1. Taken together the excellent in vitro biocompatibility profile and the favorable physicochemical characteristics of the tested polyoxyethylated calix[4]arenes give us reason to consider them as promising for further evaluation as drug delivery platforms.

Topics: Calixarenes; Cell Line, Tumor; Cell Survival; Cells, Cultured; Erythrocytes; Hemolysis; Humans; Interleukin-2; Polyethylene Glycols

The synthesis of a series of fully O-derivatised para-acyl-calix[8]arenes is described, where the acyl function is either octanoyl or hexadecanoyl. The groups attached at the phenolic face are, carboxymethoxy (anionic), carboxypropoxy (anionic), 4-sulfonatobutoxy (anionic), ethoxycarboxymethoxy (neutral), ethoxycarboxypropoxy (neutral), 2-methoxyethoxy (neutral) and 2-(2-methoxy)diethoxy (neutral). The use of specific synthetic routes has allowed complete substitution in high yields for all the compounds obtained. The interfacial properties of the compounds have been studied and stable monolayers have been obtained for certain compounds in the series having para-octanoyl substituents; all compounds studied in the series having para-hexadecanoyl substituents formed stable monolayers at the air-water interface. The interactions between O-4-sulfonatobutoxy-para-ocatanoylcalix[8]arene and a series of serum albumins have been studied by dynamic light scattering and specific adsorption of the calix-[8]-arene derivative onto the proteins observed. The anionic derivatives O-4-sulfonatobutoxy-para-ocatanoylcalix[8]arene and O-carboxymethoxy-para-ocatanoylcalix[8]arene have been shown to possess anticoagulant properties but to have no haemolytic toxicity.

Topics: Animals; Anticoagulants; Blood Coagulation; Calixarenes; Cattle; Erythrocytes; Hemolysis; Humans; Molecular Structure; Particle Size; Serum Albumin, Bovine; Solubility; Stereoisomerism; Structure-Activity Relationship; Surface-Active Agents; Time Factors

In this paper, we describe the haemolytic effect of parent para-sulphonato-calix-[n]-arenes and their derivatives bearing one pendant group at the lower rim of calix-arene towards human erythrocytes. A maximum of 30% of haemolysis has been observed for para-sulphonato-calix-[8]-arene for a concentration of 200 mM representing 300 g of calix-arene per liter of human blood, para-sulphonato-calix-[4]-arene and para-sulphonato-calix-[6]-arene show much lower haemolytic effects, 0.5 and 8%, respectively at 200 mM concentration. Coupling of a methoxy-carboxylate function at the phenolic group reduces haemolytic effects in all cases. The presence of an ethoxy-amine function increases the haemolytic behaviour for the calix-[4]-arene and calix-[6]-arene systems, but reduces the effect for the calix-[8]-arene derivatives.

Topics: Arylsulfonates; Calixarenes; Dose-Response Relationship, Drug; Drug Carriers; Erythrocytes; Hemolysis; Humans; In Vitro Techniques; Macromolecular Substances; Polycyclic Compounds; Solubility; Structure-Activity Relationship