Advances in the Physicochemical Profiling of Opioid Compounds of Therapeutic Interest

Mazák, Károly; Noszál, Béla; Hosztafi, Sándor

doi:10.1002/open.201900115

Cited by 14 publications

(8 citation statements)

References 61 publications

(127 reference statements)

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“…Supplementary Figure S4b shows that maximum sensor response was obtained at pH 7.4. NLX has an isoelectric point of 8.55 and it exists in four tautomeric forms in solution [ 51 ]. At pH 7.4, the cationic form predominates with a mole fraction of 79.6% [ 51 ], which may lead to optimal electrostatic and non-covalent interactions with the cavities formed in the sol-gel MIP.…”

Section: Resultsmentioning

confidence: 99%

A Molecularly Imprinted Sol-Gel Electrochemical Sensor for Naloxone Determination

2021

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A molecularly imprinted sol-gel is reported for selective and sensitive electrochemical determination of the drug naloxone (NLX). The sensor was developed by combining molecular imprinting and sol-gel techniques and electrochemically grafting the sol solution onto a functionalized multiwall carbon nanotube modified indium-tin oxide (ITO) electrode. The sol-gel layer was obtained from acid catalyzed hydrolysis and condensation of a solution composed of triethoxyphenylsilane (TEPS) and tetraethoxysilane (TES). The fabrication, structure and properties of the sensing material were characterized via scanning electron microscopy, spectroscopy and electrochemical techniques. Parameters affecting the sensor’s performance were evaluated and optimized. A sensor fabricated under the optimized conditions responded linearly between 0.0 µM and 12 µM NLX, with a detection limit of 0.02 µM. The sensor also showed good run-to-run repeatability and batch-to-batch performance reproducibility with relative standard deviations (RSD) of 2.5–7.8% (n = 3) and 9.2% (n = 4), respectively. The developed sensor displayed excellent selectivity towards NLX compared to structurally similar compounds (codeine, fentanyl, naltrexone and noroxymorphone), and was successfully used to measure NLX in synthetic urine samples yielding recoveries greater than 88%.

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Section: Resultsmentioning

confidence: 99%

A Molecularly Imprinted Sol-Gel Electrochemical Sensor for Naloxone Determination

2021

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“…This may indicate continued (very) slow release over much longer periods than the 30 days measured. Potentially, some of the naloxone is entrapped within the hydrophobic sandwich created by leucine pendant groups in the self-assembled peptide, or forms salt bridges due to amphiphilicity of both peptides and naloxone around neutral pH . Additionally, at higher concentrations, hydrogen bonding between drug molecules and the scaffold may occur .…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Injectable Naloxone-Releasing Hydrogels

Crowe

Siddiqui

Harbour

et al. 2020

ACS Appl. Bio Mater.

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The opioid epidemic in the United States is a serious public health crisis affecting over 1.7 million Americans. In the last two decades, almost 450 000 people have died from an opioid overdose, with nearly 20% of these deaths occurring in 2017 and 2018 alone. During an overdose, overstimulation of the μopioid receptor leads to severe and potentially fatal respiratory depression. Naloxone is a competitive μ-opioid-receptor antagonist that is widely used to displace opioids and rescue from an overdose. Here, we describe the development of a slow-release, subcutaneous naloxone formulation for potential management of opioid overdose, chronic pain, and opioid-induced constipation. Naloxone is loaded into self-assembling peptide hydrogels for controlled drug release. The mechanical, chemical, and structural properties of the nanofibrous hydrogel enable subcutaneous administration and slow, diffusion-based release kinetics of naloxone over 30 days in vitro. The naloxone hydrogel scaffold showed cytocompatibility and did not alter the β-sheet secondary structure or thixotropic properties characteristic of self-assembling peptide hydrogels. Our results show that this biocompatible and injectable self-assembling peptide hydrogel may be useful as a vehicle for tunable, sustained release of therapeutic naloxone. This therapy may be particularly suited for preventing renarcotization in patients who refuse additional medical assistance following an overdose.

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“…NMR spectra were referenced to the internal standard DSS. The water signal was suppressed by presaturation [ 44 ]. Spectra were processed using Varian VNMRj 3.2a software (Varian, Inc., NMR Systems, Palo Alto, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants

et al. 2020

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Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier protein. Hence obtaining a free amino or carboxylic group during the structural transformation is an important part of the synthesis. Namely, these groups can be used to form the requisite peptide bond between the hapten and the carrier protein. Focusing on this basic principle, six nor-morphine compounds were treated with ethyl acrylate and ethyl bromoacetate, while the prepared esters were hydrolyzed to obtain the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives which are considered as potential haptens. The next step was the coupling phase with glycine ethyl ester, but the reactions did not work or the work-up process was not accomplishable. As an alternative route, the normorphine-compounds were N-alkylated with N-(chloroacetyl)glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine side chain. The acid-base properties of these molecules are characterized in detail. In the N-carboxyalkyl derivatives, the basicity of the amino and phenolate site is within an order of magnitude. In the glycine derivatives the basicity of the amino group is significantly decreased compared to the parent compounds (i.e., morphine, oxymorphone) because of the electron withdrawing amide group. The protonation state of the carboxylate group significantly influences the basicity of the amino group. All of the glycine ester and the glycine carboxylic acid derivatives are currently under biological tests.

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Advances in the Physicochemical Profiling of Opioid Compounds of Therapeutic Interest

Cited by 14 publications

References 61 publications

A Molecularly Imprinted Sol-Gel Electrochemical Sensor for Naloxone Determination

A Molecularly Imprinted Sol-Gel Electrochemical Sensor for Naloxone Determination

Evaluation of Injectable Naloxone-Releasing Hydrogels

Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants

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