Considering the confusing biodistribution data through the literature and few reported alerts as well as our preliminary biodistribution results, we decided to evaluate the interaction and interference of the commonly present (99m) Tc (technetium-99m)-stannic oxide colloid during the direct stannous chloride (99m) Tc-labeling procedure and to assess its influence on the biodistribution pattern of amphiphilic poly(lactic-co-glycolic acid) nanoparticles. In order to confirm our thesis, beside stannous chloride, we employed two different reducing agents that don't form colloidal particles. The use of sodium borohydride was previously reported in the literature, whereas sodium dithionite was adapted for the first time in the (99m) Tc direct labeling procedure for nanoparticles. The results in our paper clearly differentiate among samples with and without colloidal impurities originating from the labeling procedure with a logical follow up of the radiochemical, physicochemical evaluation, and biodistribution studies clarifying previously reported data on stannic oxide colloidal interference. (99m) Tc-nanoparticle complex labeled with sodium dithionite as reducing agent illustrated appropriate labeling efficacy, stability, and potential for further use in biodistribution studies thus providing solution for the problem of low-complex stability when sodium borohydride is used and colloidal stannic oxide interference for stannous chloride procedure.

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Introduction: COVID-19 can be worsened by hyper-production of cytokines accompanied by increased level of oxidative stress. The aim of this study was to investigate the correlation between a set of cytokines and the markers of the oxidative stress. Methods: The levels of cytokines IL-2, IL-4, IL-6, IL8, IL-10, VEGF, IFN-γ, TNF-α, IL-1α, MCP-1 and EGF were determined by using High Sensitivity Evidence Investigator™ Biochip Array technology. The oxidative stress parameters (d-ROM, PAT, OS index) were measured in serum on FRAS5 analytical photometric system. Results: IL-6, IL-8, IL-10, VEGF, MCP-1 and EGF were significantly higher (p<0.05) in the patients with severe COVID-19 with increased levels of IL-2, IFN-y, TNF-α and IL-1α. The d-ROM, OS index, and PAT were significantly higher (p<0.05) in severe COVID-19 patients. IL-6 demonstrated the strongest correlation with all of the markers of the oxidative stress, d-ROM (r=0.9725, p=0.0001), PAT (r=0.5000, p=0.0001) and OS index (r=0.9593, p=0.012). Similar behavior was evidenced between IFN-y and d-ROM (r=0.4006, p=0.0001), PAT (r=0.6030, p=0.0001) and OS index (r=0.4298, p=0.012). Conclusion: The oxidative stress markers show good correlation with the tested cytokines which can be measured at the beginning of the disease in a primary care setting to predict the course of COVID-19.

The process of molecular self-assembly plays a crucial role in formulation of polymeric nanoparticulated drug delivery carriers as it creates the possibility for enhanced drug encapsulation and carrier surface engineering. This study aimed to develop a novel self-assembled polymeric micelles for targeted delivery in tumor cells in order to overcome not only various drawbacks of 7-ethyl-10-hydroxy camptothecin (SN-38) but also various reported limitations of other drug delivery systems, especially low drug loading and premature release. Custom synthesized amphiphilic triblock copolymer poly(acrylic acid)-poly(ɛ-caprolactone)-poly(acrylic acid) (PAA(13)-PCL(35)-PAA(13)) was used to prepare kinetically stable micelles by nanoprecipitation and modified nanoprecipitation procedure. Core-shell micelles with diameter of 120-140 nm, negative zeta potential and satisfactory drug loading were produced. The prepared formulations were stable in pH range of 3-12 and in media with NaCl concentration <1 mol/l. Screening mixed level factorial 3 × 2(2) design identified that the process temperature as well as the type of organic solvent has influence upon the efficacy of encapsulation, particle size, dissolution rate and burst release. Fourier transform infrared and differential scanning calorimetry analyses confirmed the entrapment of the active substance into the micelles. The kinetic analysis of dissolution studies revealed that the main mechanism of drug release from the prepared formulations is Fickian diffusion. Growth inhibition studies as well as DNA fragmentation assay performed on SW-480 cell lines clearly demonstrated increased growth inhibition effect and presence of fragmented DNA in cells treated with loaded micelles compared to SN-38 solution. Altogether, these results point out to potential biomedical and clinical application of PAA-PCL-PAA systems in the future.

Background: Clinical evidence suggests increased oxidative stress in COVID-19 patients and this worsened redox status could potentially contribute to the progression of the disease. Objectives: To investigate the oxidative stress we have measured oxidative stress parameters, namely, PAT (total antioxidant power, iron reducing) and d-ROMs (plasma peroxides). Additionally we have investigated their correlation with the most frequently used clinical parameters CRP, LDH, and NLR in serum from moderate and severe COVID-19 patients hospitalized in a tertiary hospital. Methods: PAT and d-ROMs were determined by analytical photometric metric method in serum from 50 hospitalized patients. For each of them, two samples were collected and analyzed immediately after collection seven days apart. Results: All patients at admission had a much higher value for plasma peroxides and a significant correlation between oxidative stress parameters and CRP, LDH, and NLR. (p<0.05), except for OS index (OSI) vs CRP in the severe group. At discharge, plasma peroxides were reduced and OSI was improved in the moderate group. Conclusion: We consider that using OSI at the beginning of COVID-19 disease presents a valuable starting point for the general assessment of oxidative stress and hence enabling a better triage of the patients in terms of disease severity.