Mesoporous chitosan nanofibers loaded with norfloxacin and coated with phenylboronic acid perform as bioabsorbable active dressings to accelerate the healing of burn wounds.

The paper reports new chitosan-based nanofibers, designed to address the healing of burn wounds. To this aim, mesoporous chitosan fiber mats were prepared by electrospinning using poly(ethylene oxide) as sacrificial additive, followed by loading with norfloxacin and coating with an antifungal agent via dynamic imine bonds. Dynamic vapor sorption experiment proved intra-fiber mesopores around 2.7 nm, and UV-vis, FTIR, and NMR spectroscopy confirmed the norfloxacin embedding and the imination reaction. SEM, AFM and POM techniques displayed semicrystalline nanofibers with average diameter around 170 nm entangled into a non-woven mat. Their mesoporous nature favored a rapid adsorption of fluids up to 17 g/g, and a biodegradation rate fitting the wound healing rate, i.e. up to 30 % mass loss in media of pH characteristic to wound exudate and total degradation in that characteristic to normal dermis. The composite fibers released the NFX and 2FPBA in a controlled manner, and showed antimicrobial activity against gram positive, gram negative and fungal strains. They had no cytotoxic effect on normal human dermal fibroblasts, and showed biocompatibility on experimental rats. The investigation of wound healing ability on second/third-degree burn model in rats revealed wound closure and total restoration of the fully functional dermis and epidermis.

Quaternized chitosan (nano)fibers: A journey from preparation to high performance applications.

The industrial production of chitosan, initiated over 50 years ago, has transformed its application across diverse industries, agriculture, and medicine. To enhance its properties, numerous chitosan derivatives have been synthesized. The quaternization of chitosan has proven beneficial, as it not only enhances its properties but also imparts water solubility, expanding its potential for a wider range of applications. Specifically, the utilization of quaternized chitosan-based nanofibers has leveraged the synergistic benefits of quaternized chitosan (including hydrophilicity, bioadhesiveness, antimicrobial, antioxidant, hemostatic, and antiviral activities, as well as ionic conductivity) in combination with the distinctive characteristics of nanofibers (such as a high aspect ratio and 3D architecture). This combination has permitted numerous possibilities, spanning from wound dressings, air and water filters, drug delivery scaffolds, antimicrobial textiles, to energy storage systems and alkaline fuel cells. In this comprehensive review, we examine the preparation methods, properties, and applications of various composite fibers containing quaternized chitosan. The advantages and disadvantages of each method and composition are meticulously summarized, while relevant diagrams and figures illustrate the key findings.

Antitumor Activity of PEGylated and TEGylated Phenothiazine Derivatives: Structure-Activity Relationship.

The paper aims to investigate the antitumor activity of a series of phenothiazine derivatives in order to establish a structure-antitumor activity relationship. To this end, PEGylated and TEGylated phenothiazine have been functionalized with formyl units and further with sulfonamide units via dynamic imine bonds. Their antitumor activity was monitored in vitro against seven human tumors cell lines and a mouse one compared to a human normal cell line by MTS assay. In order to find the potential influence of different building blocks on antitumor activity, the antioxidant activity, the ability to inhibit farnesyltransferase and the capacity to bind amino acids relevant for tumor cell growth were investigated as well. It was established that different building blocks conferred different functionalities, inducing specific antitumor activity against the tumor cells.

TEGylated Phenothiazine-Imine-Chitosan Materials as a Promising Framework for Mercury Recovery.

This paper reports new solid materials based on TEGylated phenothiazine and chitosan, with a high capacity to recover mercury ions from aqueous solutions. They were prepared by hydrogelation of chitosan with a formyl derivative of TEGylated phenothiazine, followed by lyophilization. Their structural and supramolecular characterization was carried out by 1H-NMR and FTIR spectroscopy, as well as X-ray diffraction and polarized light microscopy. Their morphology was investigated by scanning electron microscopy and their photophysical behaviour was examined by UV/Vis and emission spectroscopy. Swelling evaluation in different aqueous media indicated the key role played by the supramolecular organization for their hydrolytic stability. Mercury recovery experiments and the analysis of the resulting materials by X-ray diffraction and FTIR spectroscopy showed a high ability of the studied materials to bind mercury ions by coordination with the sulfur atom of phenothiazine, imine linkage, and amine units of chitosan.

Pegylation of phenothiazine - A synthetic route towards potent anticancer drugs.

Introduction: Cancer is a big challenge of the 21 century, whose defeat requires efficient antitumor drugs. Objectives: The paper aims to investigate the synergistic effect of two structural building blocks, phenothiazine and poly(ethylene glycol), towards efficient antitumor drugs. Methods: Two PEGylated phenothiazine derivatives were synthetized by attaching poly(ethylene glycol) of 550 Da to the nitrogen atom of phenothiazine by ether or ester linkage. Their antitumor activity has been investigated on five human tumour lines and a mouse tumor line as well, by determination of IC50. The in vivo toxicity was determined by measuring the LD50 in BALB/c mice by the sequential method and the in vivo antitumor potential was measured by the tumours growth test. The antitumor mechanism was investigated by complexation studies of zinc and magnesium ions characteristic to the farnesyltransferase enzyme, by studies of self-aggregation in the cells proximity and by investigation of the antitumor properties of the acid species resulted by enzymatic cleavage of the PEGylated derivatives. Results: The two compounds showed antitumor activity, with IC50 against mouse colon carcinoma cell line comparable with that of the traditional antitumor drugs 5-Fluorouracil and doxorubicin. The phenothiazine PEGylation resulted in a significant toxicity diminishing, the LD50 in BALB/c mice increasing from 952.38 up to 1450 mg/kg, in phenothiazine equivalents. Both compounds inflicted a 92% inhibition of the tumour growth for doses much smaller than LD50. The investigation of the possible tumour inhibition mechanism suggested the nanoaggregate formation and the cleavage of ester bonds as key factors for the inhibition of cancer cell proliferation and biocompatibility improvement. Conclusion: Phenothiazine and PEG building blocks have a synergetic effect working for both tumour growth inhibition and biocompatibility improvement. All these findings recommend the PEGylated phenothiazine derivatives as a valuable workbench for a next generation of antitumor drugs.

Water soluble PEGylated phenothiazines as valuable building blocks for bio-materials.

The paper reports a series of three new PEGylated phenothiazine derivatives which keep the potential of valuable building blocks for preparing eco-materials addressed to a large realm of fields, from bio-medicine to opto-electronics. They were synthetized by connecting the hydrophilic poly(ethylene glycol) to the hydrophobic phenothiazine via an ether, ester, or amide linking group. The successful synthesis of the targeted polymers and their purity were demonstrated by NMR and FTIR spectroscopy methods. Their capacity to self-assembly in water was studied by DLS and UV-vis techniques and the particularities of the formed aggregates were investigated by fluorescence spectroscopy, SEM, AFM, POM and UV light microscopy. The biocompatibility was assessed on normal human dermal fibroblasts and human cervical cancer cells. The synthetized compounds showed the formation of luminescent aggregates and proved excellent biocompatibility on normal cells. In addition, a concentration dependent cytotoxicity against HeLa cancer cells was noticed for the PEGylated phenothiazine containing an ester unit.