Formulation and evaluation of azithromycin-loaded silver nanoparticles for the treatment of infected wounds.

Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli. In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds.

Synthesis, Physicochemical Characterization using a Facile Validated HPLC Quantitation Analysis Method of 4-Chloro-phenylcarbamoyl-methyl Ciprofloxacin and Its Biological Investigations.

A novel derivative of ciprofloxacin (Cpx) was synthesized and characterized using various analytical techniques, including FT-IR spectroscopy, UV-Vis spectroscopy, TEM and SEM analysis, 1H NMR, 13C NMR, and HPLC analysis. The newly prepared Cpx derivative (Cpx-Drv) exhibited significantly enhanced antibacterial properties compared to Cpx itself. In particular, Cpx-Drv demonstrated a 51% increase in antibacterial activity against S. aureus and a 30% improvement against B. subtilis. It displayed potent inhibitory effects on topoisomerases II (DNA gyrase and topoisomerase IV) as potential molecular targets, with IC50 values of 6.754 and 1.913 µg/mL, respectively, in contrast to Cpx, which had IC50 values of 2.125 and 0.821 µg/mL, respectively. Docking studies further supported these findings, showing that Cpx-Drv exhibited stronger binding interactions with the gyrase enzyme (PDB ID: 2XCT) compared to the parent Cpx, with binding affinities of -10.3349 and -7.7506 kcal/mole, respectively.

Characterization and Bio-Evaluation of the Synergistic Effect of Simvastatin and Folic Acid as Wound Dressings on the Healing Process.

Wound healing is a significant healthcare problem that decreases the patient's quality of life. Hence, several agents and approaches have been widely used to help accelerate wound healing. The challenge is to search for a topical delivery system that could supply long-acting effects, accurate doses, and rapid healing activity. Topical forms of simvastatin (SMV) are beneficial in wound care. This study aimed to develop a novel topical chitosan-based platform of SMV with folic acid (FA) for wound healing. Moreover, the synergistic effect of combinations was determined in an excisional wound model in rats. The prepared SMV-FA-loaded films (SMV-FAPFs) were examined for their physicochemical characterizations and morphology. Box-Behnken Design and response surface methodology were used to evaluate the tensile strength and release characteristics of the prepared SMV-FAPFs. Additionally, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction pattern (XRD), and animal studies were also investigated. The developed SMV-FAPFs showed a contraction of up to 80% decrease in the wound size after ten days. The results of the quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant upregulation of dermal collagen type I (CoTI) expression and downregulation of the inflammatory JAK3 expression in wounds treated with SMV-FAPFs when compared to control samples and individual drug treatments. In summary, it can be concluded that the utilization of SMV-FAPFs holds great potential for facilitating efficient and expeditious wound healing, hence presenting a feasible substitute for conventional topical administration methods.

Development of Novel Nano-Sized Imine Complexes Using Coriandrum sativum Extract: Structural Elucidation, Non-Isothermal Kinetic Study, Theoretical Investigation and Pharmaceutical Applications.

A new Schiff base (H2L) generated from sulfamethazine (SMT), as well as its novel micro- and nanocomplexes with Ni(II) and Cd(II) metal ions, have been synthesized. The proposed structures of all isolated solid compounds were identified with physicochemical, spectral, and thermal techniques. Molar conductance studies confirmed that the metal complexes are not electrolytic. The molecular geometry located at the central metal ion was found to be square planar for the NiL2 and tetrahedral for the CdL2 complexes. The kinetic and thermal parameters were obtained using the Coats and Redfern approach. Coriandrum sativum (CS) in ethanol was used to create the eco-friendly Ni and Cd nanocomplexes. The size of the obtained nanoparticles was examined using PXRD and TEM, and found to be in the sub-nano range (3.07-4.61 nm). Furthermore, the TEM micrograph demonstrated a uniform and homogeneous surface morphology. The chemistry of the prepared nanocomplexes was studied using TGA and TEM techniques. The effect of temperature on the prepared nanocomplexes' size revealed a decrease in size by heating. Furthermore, the nanocomplexes' antimicrobial and anticancer properties were evaluated. The outcomes demonstrated that the nanocomplexes exhibited better antimicrobial properties. Moreover, the antitumor results showed that after heating, the Ni nanocomplex exhibited a substantial antitumor activity (IC50 = 1.280 g/mL), which was higher than the activity of cis-platin (IC50 = 1.714 g/mL). Finally, molecular-docking studies were performed to understand the evaluated compounds' ability to bind to methionine adenosyl-transferases (PDB ID: 5A19) in liver cancer and COVID-19 main protease (PDB ID: 6lu7) cell-proteins. The findings reveal that [NiL2]·1.5H2O2 has a higher binding energy of -37.5 kcal/mol with (PDB ID: 5A19) cell protein.

In vitro and in vivo synergistic wound healing and anti-methicillin-resistant Staphylococcus aureus (MRSA) evaluation of liquorice-decorated silver nanoparticles.

The multi-drug resistant Staph. aureus strain, Methicillin-resistant Staphylococcus aureus (MRSA), is an emerging pathogen that could penetrate skin cuts and wounds, causing a life-threatening condition. The green biosynthesis of silver nanoparticles with liquorice extract has been demonstrated over several years for anticancer and antioxidant effects, as well as antibacterial effect against both Gram-positive and Gram-negative bacteria. The study was designed to evaluate the synergistic in vivo and in vitro wound healing and anti-MRSA activity of decorated liquorice silver nanoparticles (LD-AgNPs). The LD-AgNPs were prepared by thoroughly mixing diluted liquorice extract with AgNO3 at room temperature. The prepared nanoparticles were characterized by size measurement, IR spectroscopy, TEM imaging, and X-ray diffraction. The in vitro and in vivo antibacterial and wound healing testing were also performed. The obtained LD-AgNPs were spherical in shape and had a hydrodynamic size of about 50.16 ± 5.37 nm. Moreover, they showed potent antibacterial activity against Gram-positive and Gram-negative resistant bacteria, produced a significantly higher level of procollagen type I compared to either liquorice extract or standard silver sulfadiazine, and promoted the wound healing process in rabbits. The formulation of silver nanoparticles with liquorice extract showed synergetic effects in enhancing the treatment of wounds, with significant antibacterial activity against E. coli and MRSA.

A Novel C@Fe@Cu Nanocomposite Loaded with Doxorubicin Tailored for the Treatment of Hepatocellular Carcinoma.

High mortality and morbidity rates are related to hepatocellular carcinoma (HCC), which is the most prevalent type of liver cancer. A new vision for cancer treatment and cancer cell targeting has emerged with the application of nanotechnology, which reduces the systemic toxicity and adverse effects of chemotherapy medications while increasing their effectiveness. It was the goal of the proposed work to create and investigate an anticancer C@Fe@Cu nanocomposite (NC) loaded with Doxorubicin (DOX) for the treatment of HCC. Scanning and transmission electron microscopes (SEM and TEM) were used to examine the morphology of the produced NC. The formulation variables (DOX content, C@Fe@Cu NC weight, and stirring speed) were analyzed and optimized using Box-Behnken Design (BBD) and Response Surface Methodology (RSM). Additionally, X-ray diffraction patterns (XRD) and Fourier Transform Infrared (FTIR) were investigated. Doxorubicin and DOX- loaded C@Fe@Cu NC (DOX-C@Fe@Cu NC) were also assessed against HEPG2 cells for anticancer efficacy (Hepatic cancer cell line). The results revealed the formation of C@Fe@Cu NC with a mean size of 7.8 nm. A D-R model with a mean size of 24.1 nm best fits the adsorption behavior of DOX onto the C@Fe@Cu NC surface. DOX-C@Fe@Cu NC has also been demonstrated to have a considerably lower IC50 and higher cytotoxicity than DOX alone in an in vitro investigation. Therefore, DOX-C@Fe@Cu NC is a promising DOX delivery vehicle for the full recovery of HCC.

Cefotaxime removal enhancement via bio-nanophotocatalyst α-Fe2O3 using photocatalytic degradation technique and its echo-biomedical applications.

The present paper evaluates the photocatalytic degradation (PCD) performance of the biofabricated hematite nanoparticles (α-HNPs) for the degradation approach of the Cefotaxime (Cfm). The optimum pH of the solution to achieve the best PCD was found to be 10.5. The kinetics study for the PCD of the Cfm via α-HNPs has been investigated and the reaction was found to be fellow pseudo-first-order at R2 = 0.992. The mass loading impact of α-HNPs was investigated and estimated for the maximum degradation of Cfm 0.4 mg/mL. UV-Vis confirmed that α-HNPs had a direct transition bandgap at 3.78 eV at a maximum absorption wavelength of 362 nm with suspension stability for 7 days. The probable mechanism of the Cfm PCD via α-HNPs and the degradation pathway was conducted. The validation of the suspension stability of the α-HNPs (-68.6 ± 11.8 mV) was determined using the zeta potential investigation test. XRD investigation was conducted after Cfm PCD showing an average crystallite size of 27.0 nm. XRD, TEM, SEM, EDX, and FT-IR analyses have been conducted for the α-HNPs before and after Cfm PCD confirming the high efficiency for the reusability of the current biocatalyst α-HNPs for further use. TEM results of the particle sizes of α-HNPs were found at 19.2 ± 4.4 and 20.6 ± 7.4 nm respectively before and after Cfm PCD. The efficiency of the Cfm PCD was found to be 99.1% after 6 h. High potent as an antibacterial agent of α-HNPs was investigated either α-HNPs alone or after its PCD activity against Cfm. The antibacterial activity revealed high sensitivity, especially toward Gram-positive species indicating its promising ability against pathogenic issues. Interestingly, Cfm@α-HNPs showed superior anti-proliferative activity as tested by MTT assay and were able to induce apoptosis in MCF7 and HepG2 cell lines using the flow cytometry technique at 20.7% and 17% respectively. Also, The IC50 of hydrogen peroxide scavenging was estimated and it was manifested that 635.8 and 665.6 µg/mL of α-HNPs before and after the PCD process of Cfm respectively.

Tailoring of Novel Azithromycin-Loaded Zinc Oxide Nanoparticles for Wound Healing.

Skin is the largest mechanical barrier against invading pathogens. Following skin injury, the healing process immediately starts to regenerate the damaged tissues and to avoid complications that usually include colonization by pathogenic bacteria, leading to fever and sepsis, which further impairs and complicates the healing process. So, there is an urgent need to develop a novel pharmaceutical material that promotes the healing of infected wounds. The present work aimed to prepare and evaluate the efficacy of novel azithromycin-loaded zinc oxide nanoparticles (AZM-ZnONPs) in the treatment of infected wounds. The Box-Behnken design and response surface methodology were used to evaluate loading efficiency and release characteristics of the prepared NPs. The minimum inhibitory concentration (MIC) of the formulations was determined against Staphylococcus aureus and Escherichia coli. Moreover, the anti-bacterial and wound-healing activities of the AZM-loaded ZnONPs impregnated into hydroxyl propyl methylcellulose (HPMC) gel were evaluated in an excisional wound model in rats. The prepared ZnONPs were loaded with AZM by adsorption. The prepared ZnONPs were fully characterized by XRD, EDAX, SEM, TEM, and FT-IR analysis. Particle size distribution for the prepared ZnO and AZM-ZnONPs were determined and found to be 34 and 39 nm, respectively. The mechanism by which AZM adsorbed on the surface of ZnONPs was the best fit by the Freundlich model with a maximum load capacity of 160.4 mg/g. Anti-microbial studies showed that AZM-ZnONPs were more effective than other controls. Using an experimental infection model in rats, AZM-ZnONPs impregnated into HPMC gel enhanced bacterial clearance and epidermal regeneration, and stimulated tissue formation. In conclusion, AZM -loaded ZnONPs are a promising platform for effective and rapid healing of infected wounds.

Novel Green Biosynthesis of 5-Fluorouracil Chromium Nanoparticles Using Harpullia pendula Extract for Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is the third highest major cause of morbidity and mortality worldwide. Hence, many strategies and approaches have been widely developed for cancer treatment. This work prepared and evaluated the antitumor activity of 5-Fluorouracil (5-Fu) loaded chromium nanoparticles (5-FuCrNPs). The green biosynthesis approach using Harpullia (H) pendula aqueous extract was used for CrNPs preparation, which was further loaded with 5-Fu. The prepared NPs were characterized for morphology using scanning and transmission electron microscopes (SEM and TEM). The results revealed the formation of uniform, mono-dispersive, and highly stable CrNPs with a mean size of 23 nm. Encapsulation of 5-Fu over CrNPs, with a higher drug loading efficiency, was successful with a mean size of 29 nm being produced. In addition, Fourier transform infrared (FTIR) and X-ray diffraction pattern (XRD) were also used for the investigation. The drug 5-Fu was adsorbed on the surface of biosynthesized CrNPs in order to overcome its clinical resistance and increase its activity against CRC cells. Box-Behnken Design (BBD) and response surface methodology (RSM) were used to characterize and optimize the formulation factors (5-Fu concentration, CrNP weight, and temperature). Furthermore, the antitumor activity of the prepared 5-FuCrNPs was tested against CRC cells (CACO-2). This in vitro antitumor study demonstrated that 5-Fu-loaded CrNPs markedly decreased the IC50 of 5-Fu and exerted more cytotoxicity at nearly all concentrations than 5-Fu alone. In conclusion, 5-FuCrNPs is a promising drug delivery system for the effective treatment of CRC.

Biosynthesis, Characterization, and Wound-Healing Activity of Phenytoin-Loaded Copper Nanoparticles.

Wound-healing is a very complex and evolutionary process that involves a great variety of dynamic steps. Although different pharmaceutical agents have been developed to hasten the wound-healing process, the existing agents are still far from optimal. The present work aimed to prepare and evaluate the wound-healing efficacy of phenytoin-loaded copper nanoparticles (PHT-loaded CuNPs). CuNPs were biosynthesized using licorice aqueous extract. The prepared CuNPs were loaded with PHT by adsorption, characterized, and evaluated for wound-healing efficiency. Results showed that both plain and PHT-loaded CuNPs were monodisperse and exhibited a cubic and hexagonal morphology. The mechanism by which PHT was adsorbed on the surface of CuNPs was best fit by the Langmuir model with a maximum loaded monolayer capacity of 181 mg/g. The kinetic study revealed that the adsorption reaction followed the pseudo-second order while the thermodynamic parameters indicated that the adsorption process was physical in nature and endothermic, and occurred spontaneously. Moreover, the in vivo wound-healing activity of PHT-loaded CuNP impregnated hydroxypropylmethyl cellulose (HPMC) gel was carried out using an excisional wound model in rats. Data showed that PHT-loaded CuNPs accelerated epidermal regeneration and stimulated granulation and tissue formation in treated rats compared to controls. Additionally, quantitative real-time polymerase chain reaction (RT-PCR) analysis showed that lesions treated with PHT-loaded CuNPs were associated with a marked increase in the expression of dermal procollagen type I and a decrease in the expression of the inflammatory JAK3 compared to control samples. In conclusion, PHT-loaded CuNPs are a promising platform for effective and rapid wound-healing.

In vitro and in vivo characterization of domperidone-loaded fast dissolving buccal films.

The delivery of drugs via fast dissolving films is an effective alternative for drugs with low bioavailability when administered by other routes. This is the case of domperidone (DMP) an anti-emetic drug with low water solubility and vulnerable to extensive first-pass effect. To overcome these limitations, in this work, we designed and produced fast dissolving muco-adhesive buccal films of domperidone using varying amount polyvinylpyrrolidone (PVP K-90) using the solvent casting method. Films loaded with more than 10% of drug were not homogenous and opaque as indicated by white patches of drug in the film matrix. Formulation of DMP in the film form resulted in conversion of the drug from crystalline state to the semi-crystalline state as indicated by X-ray powder diffraction analysis. Moreover, about 40% of drug loaded within the films was released during the first five minutes compared to only about only 6.5% of pure drug in drug dissolution assays in vitro. In vivo pharmacokinetics analysis revealed that the DMP-loaded film had higher maximum plasma concentration (Cmax) and shorter time to reach Cmax (Tmax) than a commercially available tablet formulation. In conclusion, the produced DMP buccal film formulation showed high absorption rate, rapid onset of action, and improved bioavailability compared with the conventional tablet. Our findings may support the development of novel dosage forms for the transmucosal delivery of DMP for convenient, rapid, and effective treatment of nausea and vomiting.