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Niosomes could increase the efficacy of the irrigants by providing a controlled drug release. Incorporating niosomes into an in situgel matrix maximizes the drug retention time in the root canal system. The focus of this study was the fabrication and characterization of a niosomal in situgel system for delivering chlorhexidine to root canals. For this aim, chlorhexidine-loaded niosomes were optimized by evaluating the impacts of surfactant type, surfactant to cholesterol ratio, lipid to drug weight ratio, and ethanol concentration on particle size and entrapment efficiency (EE) using an experimental design. The in situgels were also optimized with the aid of an experimental design by identifying the effects of chitosan and β-glycerophosphate concentrations as well as the solution stirring time on the gelation time and gelation temperature. The optimum niosomal nanoformulation showed an average particle size of 115 nm, EE% of ∼80 %, and PDI of 0.1. The optimum in situgels showed the lowest gelation time and appropriate gelation temperature (60 s and 29 °C, respectively). The in vitrorelease studies showed that niosomal in situgels successfully sustained the release of ∼97 % of chlorhexidine over 144 h with Higuchi kinetics. Furthermore, the biological evaluations revealed that the niosomal in situgels were cytocompatible. The system also exhibited antibacterial activity against Enterococcus faecalisbacteria, Streptococcus mutans, and Aggregatibacter actinomycetemcomitansby respectively showing 18.0, 33.3, and 48.3 mm inhibition zones in the agar well diffusion test. Overall, the results indicated that niosome-embedded in situgels showed promising potential for antimicrobial delivery to root canals.

Graphical Abstract:

Graphical Abstract:

Objective: Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14α-demethylase (CYP51). Nearly all azole antifungal agents are Nsubstituted azoles. In addition, an azolylphenalkyl pharmacophore is uniquely shared by all azole antifungals. Due to the importance of nitrogen atom of azoles (N-3 of imidazole and N-4 of triazole) in coordination with heme in the binding site of the enzyme, here a group of N- un-substituted azoles in which both nitrogen are un-substituted was reported. Materials and Methods: Designed compounds were synthesized by the reaction of imidazole-4- carboxaldehyde with appropriate arylamines and subsequently reduced to desired amine derivatives. Antifungal activity against Candida albicans and Saccharomyces cervisiae was done using a broth micro-dilution assay. Docking studies were done using AutoDock. Results: Antimicrobial evaluation revealed that some of these compounds exhibited moderate antimicrobial activities against tested pathogenic fungi, wherein compounds 3, 7, and 8 were potent. Docking studies propose that all of the prepared azoles interacted with 14α-DM, wherein azoleheme coordination played the main role in drug-receptor interaction. Conclusion: Our results offer some useful references for molecular design performance or modification of this series of compounds as a lead compound to discover new and potent antimicrobial agents.

In past decades, alginate-based multilayer microcapsules have been given important attention in various pharmaceutical investigations. Alginate-poly l lysine-alginate (APA) is studied the most. Due to the similarity between the structure of polyethyleneimine (PEI) and poly-L-lysine (PLL) and also lower price of PEI than PLL, this study was conducted to compare the efficacy of linear (LPEI) and branch (BPEI) forms of PEI with PLL as covering layers in fabrication of microcapsules. The microcapsules were fabricated using electrostatic bead generator and their shape/size, surface roughness, mechanical strength, and interlayer interactions were also investigated using optical microscopy, AFM, explosion test and FTIR, respectively. Furthermore, cytotoxicity was evaluated by comparing the two anionic final covering layers alginate (Alg) and sodium cellulose sulphate (NCS) using MTT test. BPEI was excluded from the rest of the study due to its less capacity to strengthen the microcapsules and also the aggregation of the resultant alginate-BPEI-alginate microcapsules, while LPEI showed properties similar to PLL. MTT test also showed that NCS has no superiority over Alg as final covering layer. Therefore, it is concluded that, LPEI could be considered as a more cost effective alternative to PLL and a promising subject for future studies.

Background: Bacterial resistance to the available antibiotics is a life threatening issue and researchers are trying to find new drugs to overcome this problem. Amongst the different structural classes, thiazolidinone-4-one, as a new effective pharmacophore against various bacteria, has been introduced. Objective: A new series of 2-(5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole-2-ylimino)-5-arylidenethiazolidin- 4-one derivatives were designed and synthesized as new antibacterial agents. Method: Target compounds were synthesized during 5 steps and their in vitro antibacterial and anti-H. pylori activities were evaluated. The interaction of the most active derivatives with the probable targets was assessed by Auto Dock 4.2 Program. Results: The results showed that the most potent compounds, 18, 22 and 23, displayed antibacterial activity versus S.aureus, S.epidermidis, B.cereus and B.subtilis (MIC, 1.56-12.5 μg/mL) and none of the derivatives were active on tested Gram-negative bacteria. Compound 12 in all considered doses and compounds 10, and 27 had strong anti-H. pylori activity (inhibition zone >20 mm) in 25 μg disc. Docking studies determined suitable interactions and affinity of potent compounds with bacterial MUR B and H. pylori urease enzymes. Conclusion: According to the results most of the derivatives are effective anti-bacterial agents and docking evaluation confirmed their possible mechanisms of actions as MURB and Urease inhibitors.

Recombinant human erythropoietin (rhEPO) is an important therapeutic protein that is used to treat anemia. To improve the pharmacokinetic properties of proteins, structure modification with PEG molecules has been considered as a promising approach. However, PEGylation has been found to reduce the bioactivity of proteins. To overcome this challenge, a recently developed Self-assembly PEGylation Retaining Activity (SPRA) technology has been proposed to increase the blood retention of proteins without loss of activity. In this investigation, we used this approach and synthesized SPRA-rhEPO inclusion complex via a host-guest interaction. The inclusion complex was prepared by reacting adamantane (AD) modified rhEPO and monoPEGylated β-cyclodextrin (β-CD) with a molar ratio of 1:1. Different analytical techniques including FT-IR, powder XRD, 1H NMR spectroscopy, TGA, DSC, and MALDI-TOF mass spectrometry were employed and the results confirmed the formation of the inclusion complex.

Low dissolution rate of pharmaceutical agents with poor water-solubility limits their bioavailability after oral administration. These two parameters are pivotal when a fast onset of action required which could be the case for meloxicam (MLX), an anti-inflammatory and pain reliever compound. In the present study, the effects of various solvents and method of crystallization were investigated to modify the physicochemical properties and dissolution of MLX crystals. X-ray diffractometry, infrared spectrophotometry and differential scanning calorimetry were used to investigate the crystalline characteristics of the particles. Dissolution, particle size, solubility, contact angle and morphology of crystals were also evaluated. It was found that the type of solvent and crystallization methods modified the shape of crystals from polyhedral irregular to prismatic particles. The results ruled out any polymorphic changes occurred during the processes for most samples. The dissolution rate of MLX was improved by recrystallization and the best dissolution performance was observed for crystals prepared by anti-solvent precipitation in the presence of acetone, ethanol, and propanol with a 2-3-fold increase in dissolution efficiency than that of the parent drug. This could be related to the decreased particle size, lower contact angle, improved wettability and crystalline modifications.