Development of a Novel Histatin-5 Mucoadhesive Gel for the Treatment of Oral Mucositis: In Vitro Characterization and In Vivo Evaluation.

Antimicrobial peptides have appeared to be promising candidates for therapeutic purposes due to their broad antimicrobial activity and non-toxicity. Histatin-5 (Hst-5) is a notable salivary antimicrobial peptide that exhibited therapeutic properties in the oral cavity. Oral mucositis is an acute inflammation of the oral cavity, following cancer therapy. The current treatment methods of oral mucositis have low effectiveness. The aim of this study was to design, formulate and characterize a mucoadhesive gel delivery system for Hst-5 usage in the treatment of oral mucositis. Carbopol 934 and hydroxypropyl methylcellulose (HPMC) have been used in the development of a Hst-5 mucoadhesive gel that was optimized by using Box-Behnken design. The optimized formulation was evaluated in-vitro, based on mucoadhesive strength, viscoelasticity, spreadability, release rate, peptide secondary structure analysis, antimicrobial activity, and storage stability. The efficacy of Hst-5 gel was assessed in vivo in a chemotherapy-induced mucositis model. The results showed a sustained release of Hst-5 from the new formulation. Hst-5 gel exerted antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The histopathological, immunohistochemical and statistical analysis showed that the Hst-5 gel had wound healing activity in vivo. The findings of this study indicate that the mentioned compound possesses promising potential as a novel and efficient therapeutic agent in managing oral mucositis. Moreover, the results suggest that the compound is commercially feasible for further development and utilization.

Recent Advances in Oral Mucoadhesive Drug Delivery.

The oral cavity is one of the most important routes for local and systemic drug delivery, as it has a large surface, high permeability, and rich blood supply. Oral mucosal drug delivery has some advantages, such as enhancing bioavailability, preventing first-pass metabolism, reducing dose frequency, and non-invasiveness. In recent years, notable oral mucoadhesive patents were introduced to the pharmaceutical field, which indicates promising potentials for therapeutic purposes. Oral mucosal drug delivery can play a key role to deliver the biological drugs, such as antimicrobial peptides. This article gives an overview of oral mucoadhesive drug delivery systems and provides basic principles for the researchers to overcome the problems associated with the formulation design.

Laccase-loaded magnetic dialdehyde inulin nanoparticles as an efficient heterogeneous natural polymer-based biocatalyst for removal and detoxification of ofloxacin.

An efficient heterogeneous natural polymer-based biocatalyst was fabricated through the immobilization of laccase onto dialdehyde inulin (DAI)-coated silica-caped magnetic nanoparticles (laccase@DAI@SiO2@Fe3O4⋅MNPs). The carrier was developed using SiO2@Fe3O4⋅MNPs and functionalized with DAI. The construction of immobilized laccase was confirmed by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. Immobilization yield and efficiency were calculated as 61.0 ± 0.3% and 93.0 ± 0.6%, respectively. The immobilized laccase maintained 50% and 85% of its relative activity after 25 repeated cycles and 20 days of storage at 4 °C, respectively. The prepared biocatalyst effectively eliminated ofloxacin, a fluoroquinolone-type antibiotic, with a 63% removal capacity. Besides, antimicrobial activity study on some soil microorganisms involved in the biodegradation of xenobiotics revealed that the laccase-treated ofloxacin resulted in less toxic metabolites. The obtained data indicated that the fabricated biocatalyst is promising for the removal of ofloxacin or other analogs of fluoroquinolones in the environment.

Design, synthesis, and α-glucosidase-inhibitory activity of phenoxy-biscoumarin-N-phenylacetamide hybrids.

Thirteen new phenoxy-biscoumarin-N-phenylacetamide derivatives (7a-m) were designed based on a molecular hybridization approach as new α-glucosidase inhibitors. These compounds were synthesized with high yields and evaluated in vitro for their inhibitory activity against yeast α-glucosidase. The obtained results revealed that a significant proportion of the synthesized compounds showed considerable α-glucosidase-inhibitory activity in comparison to acarbose as a positive control. Representatively, 2-(4-(bis(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)phenoxy)-N-(4-bromophenyl)acetamide (7f), with IC50 = 41.73 ± 0.38 µM against α-glucosidase, was around 18 times more potent than acarbose (IC50 = 750.0 ± 10.0 µM). This compound was a competitive α-glucosidase inhibitor. Molecular modeling and dynamic simulation of these compounds confirmed the obtained results through in vitro experiments. Prediction of the druglikeness/ADME/toxicity of the compound 7f and comparison with the standard drug acarbose showed that the new compound 7f was probably better than the standard drug in terms of toxicity.

Novel N'-substituted benzylidene benzohydrazides linked to 1,2,3-triazoles: potent α-glucosidase inhibitors.

Herein, various N'-substituted benzylidene benzohydrazide-1,2,3-triazoles were designed, synthesized, and screened for their inhibitory activity toward α-glucosidase. The structure of derivatives was confirmed using 1H- and 13C-NMR, FTIR, Mass spectrometry, and elemental analysis. All derivatives exhibited good inhibition with IC50 values in the range of 0.01 to 648.90 µM, compared with acarbose as the positive control (IC50 = 752.10 µM). Among them, compounds 7a and 7h showed significant potency with IC50 values of 0.02 and 0.01 µM, respectively. The kinetic study revealed that they are noncompetitive inhibitors toward α-glucosidase. Also, fluorescence quenching was used to investigate the interaction of three inhibitors 7a, 7d, and 7h, with α-glucosidase. Accordingly, the binding constants, the number of binding sites, and values of thermodynamic parameters were determined for the interaction of candidate compounds toward the enzyme. Finally, the in silico cavity detection plus molecular docking was performed to find the allosteric site and key interactions between synthesized compounds and the target enzyme.

Hybridization of laccase with dendrimer-grafted silica-coated hercynite-copper phosphate magnetic hybrid nanoflowers and its application in bioremoval of gemifloxacin.

Laccase was successfully hybridized with polyamidoamine (PAMAM) dendrimer-grafted silica-coated hercynite-copper phosphate magnetic hybrid nanoflowers (MHNFs) to increase the catalytic performance of the enzyme and apply in an effective bioremoval of gemifloxacin. For this purpose, the magnetic nanoparticles (MNPs) of hercynite were covered with a silica layer, and the core-shell SiO2@hercynite was then modified with PAMAM dendrimer to increase the surface area of the carrier for the enzyme attachment. Subsequently, the whole complex was hybridized with laccase and copper phosphate to attain a large surface area (104.3 m2 g-1). The fabricated MHNFs acquired the entrapment yield and efficiency of 90 ± 3% and 66 ± 5%, respectively. The catalytic activity of the fabricated biocatalyst was remained up to 50% after 13 reusability cycles. Approximately 90% of gemifloxacin was removed by the constructed MHNFs after 3 h incubation by adsorption and degradation mechanisms. The biotransformation products were then identified, and degradation pathways were proposed as defluorination, decarboxylation, elimination of a cyclopropyl group, and cleavage of the pyrrolidine moiety. Furthermore, the toxicity of gemifloxacin was effectively diminished against some bacterial strains.