Voltammetric analysis of pholcodine on graphene-modified GNPs/PTs with green assessment.

Pholcodine, an anti-tussive medication widely used as an over-the-counter, OTC drug, has recently faced restrictions in several countries. This paper presents a sensitive electrochemical approach for pholcodine detection. The electrochemical method involved fabricating a graphene nanoplatelets electrode, incorporating polythiophene nanospheres polymer to promote electron transfer and increase the activated surface area. Characterization of the fabricated electrode was performed using transmission electron microscopy, ATR-Fourier-transform infrared spectroscopy, X-ray crystallography, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The electrochemical behavior of pholcodine with the fabricated electrode was investigated using cyclic voltammetry, chronoamperometry, square wave voltammetry (SWV), and differential pulse voltammetry (DPV). The developed electrode led to a linear response for pholcodine ranging from 10 to 45 mg/L with detection limits of 1.41 and 1.51 mg/mL for SWV and DPV, respectively and quantification limits of 4.27 and 4.57 mg/L for SWV and DPV, respectively. The proposed method has accurately recovered pholcodine in spiked serum samples with a recovery percentage ranging from 1.2 to 2.9%. The optimized method is found to be accurate, precise, and robust by applying validation parameters provided by International Council for Harmonization. Two green metrics were computed to assess the method's greenness, the findings showed that the developed method is environmentally friendly with minimum sample preparation steps.

Simultaneous analysis of the of levamisole with triclabendazole in pharmaceuticals through developing TLC and HPLC-PDA chromatographic techniques and their greenness assessment using GAPI and AGREE methods.

Two simple and rapid chromatographic methods were developed and validated for the analysis of levamisole and triclabendazole simultaneously in pure and pharmaceutical products. The first method is thin-layer chromatography (TLC) with densitometry, and the second method is high-performance liquid chromatography with PDA detection (HPLC-PDA). A Hypersil BDS C18 column with dimensions of 4.6 × 150 mm and a particle size of 5 µm was used in the HPLC-PDA method. An isocratic condition was used to carry out the separation, and the mobile phase was made up of acetonitrile and a 0.03 M potassium dihydrogen phosphate buffer in double-distilled water. The ratio of the mobile phase preparation was 70:30 (v/v), and the flow rate was 1 mL/min. A wavelength of 215 nm was employed for analyte detection. Precoated silica gel 60 F254 aluminium plates were used for the TLC method's separation. Mobile phase was made of ethyl acetate, hexane, methanol, and ammonia (69:15:15:1) for the separation. The detection wavelength selected was 215 nm. According to the International Council for Harmonization (ICH) guidelines, the proposed methods were validated and it was found that the two chromatographic methods are accurate, precise, and linear for both compounds in the range of 3.75-37.5 and 6-60 mg/L for the HPLC method for levamisole and triclabendazole, respectively and in the range of 2-14 µg/spot for the TLC method. The developed methods greenness profile was assessed using AGREE and ComplexGAPI tools.

Oral proniosomal amitriptyline and liraglutide for management of diabetic neuropathy: Exceptional control over hyperglycemia and neuropathic pain.

Exploitation of nanocarriers provides a compartment for enclosing drugs to protect them from degradation and potentiate their therapeutic efficiency. In the current study, amitriptyline- and liraglutide-loaded proniosomes were constructed for management of diabetic neuropathy, a serious complication associated with diabetes, that triggers spontaneous pain in patients and results in impaired quality of life. The developed therapeutic proniosomes were extensively characterized via dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and Fourier transform-infrared spectroscopy. High entrapment efficiency could be attained for both drugs in the proniosomes, and the reconstituted amitriptyline- and liraglutide-loaded niosomes possessed spherical morphology and particle sizes of 585.3 nm and 864.4 nm, respectively. In a diabetic neuropathy rat model, oral administration of the developed amitriptyline- and liraglutide-loaded proniosomes significantly controlled blood glucose levels, reduced neuropathic pain, oxidative stress and inflammatory markers, and improved histological structure of the sciatic nerve as compared to the oral and subcutaneous administration of amitriptyline and liraglutide, respectively. Loading of the tricyclic antidepressant amitriptyline and the antidiabetic peptide liraglutide into proniosomes resulted in exceptional control over hyperglycemia and neuropathic pain, and thus could provide an auspicious delivery system for management of neuropathic pain and control of blood glucose levels.

Morphologic design of nanogold carriers for a carbonic anhydrase inhibitor: Effect on ocular retention and intraocular pressure.

Morphologic design of nanomaterials for a diversity of biomedical applications is of increasing interest. The aim of the current study is to construct therapeutic gold nanoparticles of different morphologies and investigate their effect on ocular retention and intraocular pressure in a glaucoma rabbit model. Poly(lactic-co-glycolic acid) (PLGA)-coated nanorods and nanospheres have been synthesized and loaded with carbonic anhydrase inhibitor (CAI), and characterized in vitro for their size, zeta potential and encapsulation efficiency. Nanosized PLGA-coated gold nanoparticles of both morphologies demonstrated high entrapment efficiency (˃ 98%) for the synthesized CAI and the encapsulation of the drug into the developed nanoparticles was confirmed via Fourier transform-infrared spectroscopy. In vivo studies revealed a significant reduction in intraocular pressure upon instillation of drug-loaded nanogold formulations compared to the marketed eye drops. Spherical nanogolds exhibited a superior efficacy compared to the rod-shaped counterparts, probably due to the enhanced ocular retention of spherical nanogolds within collagen fibers of the stroma, as illustrated by transmission electron microscopy imaging. Normal histological appearance was observed for the cornea and retina of the eyes treated with spherical drug-loaded nanogolds. Hence, incorporation of a molecularly-designed CAI into nanogold of tailored morphology may provide a promising strategy for management of glaucoma.

An innovative nanoparticle-modified carbon paste sensor for ultrasensitive detection of lignocaine and its extremely carcinogenic metabolite residues in bovine food samples: Application of NEMI, ESA, AGREE, ComplexGAPI, and RGB12 algorithms.

Nowadays, veterinary medicine residues have been viewed as a major threat to food safety worldwide, especially when dealing with carcinogenic residues. Herein, we present the first differential pulse voltammetric method for the quantification of lignocaine and its carcinogenic metabolite 2,6-xylidine residues in bovine food samples, aided by five greenness and whiteness assessment tools, including NEMI, ESA, ComplexGAPI, AGREE, and RGB12. The method depends on the electrochemical oxidation after modification of the carbon paste sensor with recycled Al2O3-NPs functionalized multi-walled carbon nanoparticles. The produced sensor (Al2O3-NPs/MWCNTs/CPE) was characterized using XRD, FT-IR, EDX, SEM, and TEM. As expected, the active surface area and electron transfer processes were accelerated by the modification, resulting in ultra-sensitive quantification with detection limits of 19.00 and 13.94 nM for lignocaine and 2,6-xylidine, respectively. In terms of greenness, whiteness, sustainability, analytical effectiveness, and economic and practical considerations, the proposed method outperforms the reported methods.

Development of potent nanosized carbonic anhydrase inhibitor for targeted therapy of hypoxic solid tumors.

Overexpression of two carbonic anhydrase (CA) isoforms, CA IX and XII, in several hypoxic solid tumors provides an extracellular hypoxic microenvironment, interferes with extra- and intracellular pH regulation, thus favoring hypoxic tumor cell survival, proliferation and metastasis. In the current study, a selective inhibitor for human CA isoforms IX and XII (isatin-bearing sulfonamide, WEG-104), was incorporated into nanosized spherical niosomes at high encapsulation efficiency to allow for an enhanced and sustained antitumor activity. In vivo, administration of WEG-104 that is either free (10 mg/kg) or loaded into niosomes (5 mg/kg) into a mice model of Ehrlich ascites solid tumor resulted in comparable efficacy in terms of reduction of tumor weight and volume. Administration of WEG-104-loaded niosomes (10 mg/kg) exhibited superior antitumor activity compared to the free drug, evidenced by reduced tumor weight and volume, marked reduction in the activity of CA IX and XII, and suppression of HIF-1α and MMP-2. Moreover, prominent increase of caspase 3 and pronounced decrease in VEGF immune expression were observed in the treated animals. Hence, loading of molecularly designed compounds that targets CAs in hypoxic solid tumors into nanosized delivery systems provided an auspicious strategy for limiting solid tumor progression and malignancy.

Development of potent nanosized isatin-isonicotinohydrazide hybrid for management of Mycobacterium tuberculosis.

Inspired by the antitubercular activity of isoniazid (INH) and 5-bromoisatin, isatin-INH hybrid (WF-208) has been synthesized as a potent agent against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. In silico molecular docking studies indicated that DprE1, a critical enzyme in the synthesis of M. tuberculosis cell wall, is a potential enzymatic target for WF-208. The synthesized WF-208 was incorporated into a nanoparticulate system to enhance stability of the compound and to sustain its antimicrobial effect. Nanosized spherical niosomes (hydrodynamic diameter of ca. 500-600 nm) could accommodate WF-208 at a high encapsulation efficiency of 74.2%, and could impart superior stability to the compound in simulated gastric conditions. Interestingly, WF-208 had minimal inhibitory concentrations (MICs) of 7.8 and 31.3 µg/mL against MDR and XDR M. tuberculosis, respectively, whereas INH failed to demonstrate bacterial growth inhibition at the range of the tested concentrations. WF-208-loaded niosomes exhibited a 4-fold increase in the anti-mycobacterial activity as compared to the free compound (MIC of 1.9 vs. 7.8 µg/mL) against H37Rv M. tuberculosis, after three weeks of incubation with WF-208-loaded niosomes. Incorporation of the compound into nanosized vesicles allowed for a further increase in stability, potency and sustainability of the anti-mycobacterial activity, thus, providing a promising strategy for management of tuberculosis.

Microfluidic electrochemical immunosensor for the trace analysis of cocaine in water and body fluids.

Quick but accurate testing and on-the-spot monitoring of cocaine in oral fluids and urine continues to be an important toxicological issue. In terms of drug testing, a number of devices have been introduced into the market in recent decades, notably for workplace inspection or roadside testing. However, these systems do not always fulfill the requirements in terms of reliability, especially when low cut-off levels are required. With respect to surface water, the presence of anthropogenic small organic molecules such as prescription and over-the-counter pharmaceuticals as well as illicit drugs like cannabinoids, heroin, or cocaine, has become a challenge for scientists to develop new analytical tools for screening and on-site analysis because many of them serve as markers for anthropogenic input and consumer behavior. Here, a modular approach for the detection of cocaine is presented, integrating an electrochemical enzyme-linked immunosorbent assay (ELISA) performed on antibody-grafted magnetic beads in a hybrid microfluidic sensor utilizing flexible tubing, static chip and screen-printed electrode (SPE) elements for incubation, recognition, and cyclic voltammetry measurements. A linear response of the sensor vs. the logarithm of cocaine concentration was obtained with a limit of detection of 0.15 ng/L. Within an overall assay time of 25 minutes, concentrations down to 1 ng/L could be reliably determined in water, oral fluids, and urine, the system possessing a dynamic working range up to 1 mg/L.

Screening for cocaine on Euro banknotes by a highly sensitive enzyme immunoassay.

This study focused on quantitative detection of cocaine on Euro banknotes in Germany. A sensitive direct competitive immunoassay was developed and optimized with a limit of detection (LOD) of 5.6ng/L. Exhaustive cocaine extraction by solvent was tested using different methanol concentrations and buffered solutions. Cross-reactivity studies were performed to determine the degree of interference of cocaine metabolites with the immunoassay. Sixty-five Euro banknotes obtained from different districts in Berlin were evaluated. A 100% contamination frequency with cocaine was detected. A comparison between the amount of cocaine extracted by cotton swabbing of one square centimeter of the banknote showed a good correlation for lower contamination levels. This assay showed high sensitivity of detecting pg of cocaine per 1cm2 of one banknote by swabbing 1cm2: 0, 14, and 21pg/cm2. Moreover, three notes of different denominations revealed high cocaine concentration; 1.1mg/note, and twice 55µg/note.