Synergistic Effect of Silver Nanoparticles with Antibiotics for Eradication of Pathogenic Biofilms.

BACKGROUND: The increase in nosocomial multidrug resistance and biofilm-forming bacterial infections led to the search for new alternative antimicrobial strategies other than traditional antibiotics. Silver nanoparticles [AgNP] could be a viable treatment due to their wide range of functions, rapid lethality, and minimal resistance potential. The primary aim of this study is to prepare silver nanoparticles and explore their antibacterial activity against biofilms. METHODS: AgNPs with specific physicochemical properties such as size, shape, and surface chemistry were prepared using a chemical reduction technique, and then characterized by DLS, SEM, and FTIR. The activity of AgNPs was tested alone and in combination with some antibiotics against MDR Gram-negative and Gram-positive planktonic bacterial cells and their biofilms. Finally, mammalian cell cytotoxicity and hemolytic activity were tested using VERO and human erythrocytes. RESULTS: The findings of this study illustrate the success of the chemical reduction method in preparing AgNPs. Results showed that AgNPs have MIC values against planktonic organisms ranging from 0.0625 to 0.125 mg/mL, with the greatest potency against gram-negative bacteria. It also effectively destroyed biofilm-forming cells, with minimal biofilm eradication concentrations [MBEC] ranging from 0.125 to 0.25 mg/ml. AgNPs also had lower toxicity profiles for the MTT test when compared to hemolysis to erythrocytes. Synergistic effect was found between AgNPs and certain antibiotics, where the MIC was dramatically reduced, down to less than 0.00195 mg/ml in some cases. CONCLUSION: The present findings encourage the development of alternative therapies with high efficacy and low toxicity.

Synergistic Antibacterial Effect of ZnO Nanoparticles and Antibiotics against Multidrug-Resistant Biofilm Bacteria.

BACKGROUND: The misuse of antibiotics leads to a global increase in antibiotic resistance. Therefore, it is imperative to search for alternative compounds to conventional antibiotics. ZnO nanoparticles (Zn NP) are one of these alternatives because they are an effective option to overcome biofilm bacterial cells and a novel way to overcome multidrug resistance in bacteria. The current research study aims to characterize the efficacy of ZnO nanoparticles alone and in combination with other antibacterial drugs against bacterial biofilms. METHODS: ZnO NPs were prepared by co-precipitation method, and their anti-biofilm and antibacterial activities alone or combined with four types of broad-spectrum antibacterial (Norfloxacin, Colistin, Doxycycline, and Ampicillin) were evaluated against E. coli and S. aureus bacterial strains. Finally, the cytotoxicity and the hemolytic activity were evaluated. RESULTS: ZnO NPs were prepared, and results showed that their size was around 10 nm with a spherical shape and a zeta potential of -21.9. In addition, ZnO NPs were found to have a strong antibacterial effect against Gram-positive and Gram-negative microorganisms, with a minimum inhibitory concentration (MIC) of 62.5 and 125 µg/mL, respectively. Additionally, they could eradicate biofilmforming microorganisms at a concentration of 125 µg/m. ZnO NPs were found to be non-toxic to erythrocyte cells. Still, some toxicity was observed for Vero cells at effective concentration ranges needed to inhibit bacterial growth and eradicate biofilm-forming organisms. When combined with different antibacterial, ZnO NP demonstrated synergistic and additive effects with colistin, and the MIC and MBEC of the combination decreased significantly to 0.976 µg/mL against planktonic and biofilm strains of MDR Gram-positive bacteria, resulting in significantly reduced toxicity. CONCLUSION: The findings of this study encourage the development of alternative therapies with high efficacy and low toxicity. ZnO nanoparticles have demonstrated promising results in overcoming multi-drug resistant bacteria and biofilms, and their combination with colistin has shown a significant reduction in toxicity. Further studies are needed to investigate the potential of ZnO nanoparticles as a viable alternative to conventional antibiotics.

Enhancement of the Solubility of Asenapine Maleate Through the Preparation of Co-Crystals.

BACKGROUND: Asenapine maleate, an anti-schizophrenic drug, is a class II drug with low solubility and high permeability. This exerts a rate-limiting effect on drug bioavailability. OBJECTIVE: To improve the solubility/dissolution rate of asenapine maleate and hence the bioavailability using the co-crystal approach. METHODS: Co-crystals were prepared using the solvent evaporation method. Since the drug has Hbond acceptor count of 6, and H-bond donor count of 2, several co-formers (nicotinamide, urea, succinic, benzoic, and citric acid) were investigated in different ratios. The optimized co-crystals (drug-nicotinamide in a ratio of 1:3) were evaluated using PXRD, DSC, FTIR spectroscopy, and SEM. Additionally, in vitro dissolution and stability studies were conducted. RESULTS: Preparation of the co-crystals was successful except when citric and benzoic acids were used. PXRD patterns showed that the co-crystals were crystalline. FTIR spectroscopy confirmed the formation of H-bond between the drug and the co-former. DSC indicated a lower melting point than that of the components followed immediately by an exothermic peak, which confirmed the formation of co-crystals. SEM showed the formation of crystals with different size and habit. The dissolution of the drug from all the prepared co-crystals was almost similar and much enhanced compared to that of the unprocessed drug. The initial dissolution of the drug from the optimized batch was much faster than that from the other co-crystals and the physical mixture with the same ratio. The optimized batch exhibited long term stability. CONCLUSION: Co-crystals with improved solubility/dissolution rate of asenapine maleate were prepared successfully and were expected to enhance the bioavailability of the drug.

Release behaviour of diclofenac sodium dispersed in Gelucire and encapsulated with alginate beads.

Sustained release polymeric particles containing diclofenac sodium dispersed in Gelucire matrix and encapsulated in calcium alginate shell were prepared with different drug-to-polymer ratios and also with different concentrations of sodium alginate for a fixed drug-to-polymer ratio in an aqueous environment. Spherical particles were formed by dropping an emulsion of diclofenac sodium in Gelucire matrix, emulsified with sodium alginate, into calcium chloride solution. The gelled beads formed by ionotropic gelation of alginate with calcium ions showed sustained release of the water soluble drug in in-vitro release study. Drug release was a function of square-root of time, suggesting a matrix diffusion release pattern. The rate of release was significantly suppressed with increasing proportions of Gelucire in the mixture. Sustained and complete release was achieved with Gelucire of low melting point and low HLB value. No significant drug release occurred in a dissolution medium of pH 1.5, whereas complete release was observed at pH 6.8, consistent with considerable swelling of the alginate gel at this pH.

Determination of the mechanism of uptake of organic vapors by chitoasn.

It was of interest to investigate the possible interactions that might occur between chitosan and various compounds of different polarities using solvent vapor sorption and Fourier Transform Infrared Spectroscopy (FTIR). The sorption system was composed of a gas inlet, a 2 meter gas cell and a gas outlet. The experimental set up allowed quantification of the free vapor and therefore the amount of the sorbed vapor by chitosan powder. The BET equation was applied to the experimental data to obtain the apparent monolayer sorption capacity (Sm) and the parameter C, which is related to the heat of interaction. Results demonstrated that the surface areas obtained for chitosan from the BET analyses for heptane, 1,4-dioxane and methanol were 421, 379 and 58 m(2)/g, respectively. These values were extremely higher than the value obtained from nitrogen vapor adsorption isotherm (4.56 m(2)/g). The difference is attributed to the partitioning of these compounds into the chitosan particles. The large difference in the Sm values between the nonpolar (heptane and 1,4-dioxane) and the semipolar compounds (methanol) also suggested that the polarity of the solvent might have a significant effect on the partitioning of the these compounds into the chitosan particles. The results obtained from this study also confirmed what was previously described regarding the ability of chitosan to act as a 'fat magnet' or a 'fat sponge'.

The sorption of ketotifen fumarate by chitosan.

The purpose of this investigation was to determine the mechanism of interaction between ketotifen fumarate and chitosan at different pH values. The specific surface area of chitosan was determined using gas sorption analyzer. The sorption experiments were conducted at pH 7 and 10 using two different particle size ranges of chitosan. The solutions were prepared at constant ionic strength and buffer concentration, with only varying the pH. The rotating bottle method was used for measuring the sorption. The average specific surface areas for the two different particle size ranges of chitosan were found to be 4.56 and 0.74 m(2)/g. The Langmuir-like equation and a model independent equation were both applied to the sorption experimental data. The extent of ketotifen uptake at pH 7 for small and large particles of chitosan was found to be 1,073 and 2,204 mg/g respectively. While the extent of ketotifen uptake at pH 10 for small and large particles of chitosan was found to be 4 and 11 mg/g respectively. The aforementioned results indicated that sorption of ketotifen fumarate at pH 7 is extremely high compared to pH 10 and that the sorption increases by decreasing the specific surface area of chitosan. Based on the results obtained, the following conclusions were reached. Ketotifen might be absorbed into the bulk structure of chitosan in addition to being adsorbed on the surface and the ability of chitosan to swell at pH 7 has a significant role in increasing its uptake.