Hypericin emulsomes combined with hollow microneedles as a non-invasive photodynamic platform for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease that severely affects joint function. Despite the variability of treatment protocols, all of them are associated with severe side effects that compromise patient compliance. The main aim of the current study is to prepare localized effective RA treatment with reduced side effects by combining nanoencapsulation, photodynamic therapy (PDT) and hollow microneedles (Ho-MNs) to maximize the pharmacological effects of hypericin (HYP). To attain this, HYP-loaded emulsomes (EMLs) were prepared, characterized and administered through intradermal injection using AdminPen™ Ho-MNs combined with PDT in rats with an adjuvant-induced RA model. The prepared EMLs had a spherical shape and particle size was about 93.46 nm with an absolute entrapment efficiency. Moreover, confocal imaging indicated the interesting capability of Ho-MNs to deposit the HYP EMLs to a depth reaching 1560 µm into the subcutaneous tissue. In vivo, study results demonstrated that the group treated with HYP EMLs through Ho-MNs combined with PDT had no significant differences in joint diameter, TNF-α, IL1, HO-1, NRF2 and SD levels compared with the negative control group. Similarly, rats treated with the combination of HYP EMLs, Ho-MNs and PDT showed superior joint healing efficacy compared with the groups treated with HYP EMLs in dark, HYP ointment or HYP in microneedles in histopathological examination. These findings highlight the promising potential of photoactivated HYP EMLs when combined with Ho-MNs technology for RA management. The presented therapeutic EMLs-MNs platform could serve as a powerful game-changer in the development of future localized RA treatments.

White sustainable luminescent determination of nifuroxazide using nitrogen-sulphur co-doped carbon quantum dots nanosensor in bulk and various pharmaceutical matrices.

Nifuroxazide (NFX) is an antimicrobial agent that is frequently used as an intestinal antiseptic and recently was proven to have anticancer properties. This work employs the use of nitrogen and sulphur co-doped carbon quantum dots (NSC-dots) luminescent nanoparticles to propose a highly sensitive, sustainable, white and green spectrofluorometric method for NFX detection in bulk and pharmaceutical dosage forms. l-Cysteine and citric acid were the precursors to synthesize water soluble NSC-dots by a quick and environmentally-friendly hydrothermal process. NSC-dots' native fluorescence was measured at λem = 416 nm following excitation at 345 nm. Addition of NFX resulted in quantitative quenching of NSC-dots' luminescence, which represents the principle over which this luminescent method was based. Additionally, the mechanism of fluorescence quenching was studied and discussed. The analytical procedure was validated according to the ICH-guidelines. Linear response for NFX was obtained in the dynamic range 0.04-15 µg mL-1. The estimated NFX detection and quantification limits were 0.005 and 0.015 µg mL-1, respectively. The proposed method was employed for NFX quantification into two commercial pharmaceutical dosage forms. The calculated percentage recoveries (R%), percentage relative standard deviations (RSD%), and percentage error (Er%) were satisfactory. Comparison with other reported methods showed that the proposed method is superior in several aspects. Evaluation of the whiteness of the proposed method using the RGB 12 algorithm combined with the most widely used greenness evaluation tools, the Analytical Eco-Scale and AGREE, demonstrated its superiority and sustainability over other previously published spectrofluorimetric methods for the assay of NFX in various dosage forms.

Green "turn-off" luminescent nanosensors for the sensitive determination of desperately fluorescent antibacterial antiviral agent and its metabolite in various matrices.

Nitazoxanide (NTX) is an antimicrobial drug that was used for the treatment of various protozoa. However, during the coronavirus pandemic, NTX has been redirected for the treatment of such virus that primarily infect the respiratory tract system. NTX is now used as a broad-spectrum antiviral agent. In this study, a highly sensitive and green spectrofluorometric method was developed to detect NTX in various dosage forms and its metabolite, tizoxanide (TX), in human plasma samples using nitrogen and sulfur co-doped carbon quantum dots nanosensors (C-dots). A simple and eco-friendly hydrothermal method was used to synthetize water soluble C-dots from citric acid and l-cysteine. After excitation at 345 nm, the luminescence intensity was measured at 416 nm. Quenching of C-dots luminescence occurred upon the addition of NTX and was proportional to NTX concentration. Assessment of the quenching mechanism was performed to prove that inner filter effect is the underlying molecular mechanism of NTX quenching accomplished. After optimizing all experimental parameters, the analytical procedure was evaluated and validated using the ICH guidelines. The method linearity, detection and quantification limits of NTX were 15 × 10-3-15.00 µg/mL, 56.00 × 10-4 and 15 × 10-3 µg/mL, respectively. The proposed method was applied for the determination of NTX in its commercial pharmaceutical products; Nanazoxid® oral suspension and tablets. The obtained % recovery, relative standard deviation and % relative error were satisfactory. Comparison with other reported spectrofluorimetric methods revealed the superior sensitivity of the proposed method. Such high sensitivity permitted the selective determination of TX, the main metabolite of NTX, in human plasma samples making this study the first spectrofluorimetric method in literature that determine TX in human plasma samples. Moreover, the method greenness was assessed using both Eco-Scale and AGREE approaches to prove the superiority of the proposed method greenness over other previously published spectrofluorimetric methods for the analysis of NTX and its metabolite, TX, in various dosage forms and in human plasma samples.

Quick Test for Determination of N-Bombs (Phenethylamine Derivatives, NBOMe) Using High-Performance Liquid Chromatography: A Comparison between Photodiode Array and Amperometric Detection.

The emergence of a new class of novel psychoactive substances, N-benzyl-substituted phenethylamine derivatives so-called "NBOMes" or "Smiles", in the recreational drug market has forced the development of new sensitive analytical methodologies for their detection and quantitation. NBOMes' hallucinogenic effects mimic those of the illegal psychedelic drug lysergic acid diethylamide (LSD) and are typically sold as LSD on blotter papers, resulting in a remarkable number of fatalities worldwide. In this article, four halide derivatives of NBOMe, namely, 2-(4-fluoro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethan-1-amine, 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethan-1-amine, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethan-1-amine, and 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethan-1-amine, were detected and quantified simultaneously using a high-performance liquid chromatographic method, and two detection systems were compared: photodiode array detection (detection system I) and amperometric detection via a commercially available impinging jet flow-cell system incorporating embedded graphite screen-printed macroelectrodes (detection system II). Under optimized experimental conditions, linear calibration plots were obtained in the concentration range of 10-300 and 20-300 µg mL-1, for detection systems I and II, respectively. Detection limit (limit of detection) values were between 4.6-6.7 and 9.7-18 µg mL-1, for detection systems I and II, respectively. Both detectors were employed for the analysis of the four NBOMe derivatives in the bulk form, in the presence of LSD and adulterants commonly found in street samples (e.g. paracetamol, caffeine, and benzocaine). Furthermore, the method was applied for the analysis of simulated blotter papers, and the obtained percentage recoveries were satisfactory, emphasizing its advantageous applicability for the routine analysis of NBOMes in forensic laboratories.