Abeer Saad Hassan

Carbapenems are antibiotics that have been employed to treat infections caused by Gram-negative multidrug resistant bacteria. This investigation focused on the development of nanoconjugate green synthesized silver-chitosan nanoparticle to improve the antibacterial activity and minimize bacterial resistance to meropenem. Silver nanoparticles were developed by green synthesis method which utilized highly solubilized quercetin solid dispersion as reducing agent. The synthesized silver nanoparticles formulation underwent evaluation using different approaches. Meropenem nano-conjugate was fabricated and characterized for particle size, conjugation efficiency and in vitro release. The effectiveness of the meropenem nanoconjugate against carbapenem-resistant gram-negative bacterial isolates was investigated. Gene expression of carbapenemase producing isolates treated with nanoconjugate was monitored. The prepared meropenem nanoconjugate exhibited nanosized range (221.7±4.5 nm) and displayed conjugation efficiency of 85%. The IC50 of meropenem conjugate on the human foreskin fibroblast (HFF)-1 normal cell line was found 114.45±3.97 µg/ml indicating a negligible cytotoxic effect. Meropenem nanoconjugate was found to have the lowest minimum inhibitory concentration (MIC) when compared to free meropenem. Additionally, treatment of carbapenem-resistant bacterial cells with meropenem nanoconjugate resulted in the down regulation of carbapenem resistant gene expression. Therefore, the nano-conjugate of meropenem chitosan - silver nanoparticles presents a promising nano-platform for enhancing antibacterial efficacy and downregulating carbapenem resistance-associated genes.

Ticks are among the most significant ectoparasites of livestock and humans, posing serious health and economic risks. The growing resistance to conventional acaricides highlights the need for safer and more effective alternatives. This study aimed to evaluate the acaricidal efficacy of different ivermectin (IVM) nanoformulations against different developmental stages of Rhipicephalus sanguineus tick. Different ivermectin nanoformulations were fabricated and evaluated for their physicochemical properties. An in vitro study was performed using larval, nymphal, and adult immersion tests, followed by an in vivo trial against unfed adults using the most effective formulation. All nanoformulations showed particle sizes from 450 to 650 nm and a polydispersity index range from 0.34 to 0.65. IVM spanlastics exhibited the smallest particle size, highest encapsulation efficiency (92%), and a sustained release profile. Based on LC ₅₀ values, IVM spanlastics showed superior acaricidal activity against larvae (LC ₅₀ : 0.05%), nymphs (LC ₅₀ : 0.09%), and unfed adults (LC ₅₀ :0.16%); followed by IVM-SeNPs, where the LC ₅₀ values were 0.10, 0.23, and 0.38% for larvae, nymphs, and unfed adults, respectively. The in vivo study of IVM spanlastics demonstrated 100% mortality of adult ticks within four days after application. IVM spanlastics could be topically applied as an alternative to conventional injectable IVM to control R. sanguineus ticks. Further toxicological studies are necessary to ensure the safety of these formulations for environmental and veterinary use.

Purpose: A multitude of inflammatory cells and chemical mediators initiate a complex cascade that ultimately leads to hepatocyte death and a systemic inflammatory response. This research aimed to investigate the potential effects of sildenafil and neem (Azadirachta indica) extract, in both conventional and nanoparticle (NP) forms, in the treatment of moderate acute liver damage induced by orogastric carbon tetrachloride (CCL₄). Methods: To induce moderate acute hepatic damage a single oral dosage of CCL₄ (2.5 mL/kg body weight) was provided 24 h before euthanasia. In liver damage-induced CCL₄, sildenafil and neem extract were given in conventional and nanoparticle (PLGA or niosome) forms. To find histological anomalies and hepatic changes, behavioral, biochemical, histopathological, and immunohistochemical methods were used. Results: The findings indicated that sildenafil and/or neem extract, especially in NP combination, significantly mitigated CCL₄-induced acute moderate liver damage. Indicators of liver function, including aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), albumin, bilirubin and gamma-glutamyl transferase (GGT), shown improvement, particularly with the nanoparticulation of both therapies. Treatment, particularly in NP forms, improved the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase activity (GPx) in liver tissues. A significant reduction in NF-κB expression in hepatic tissue was shown in treatment groups. Also, medication resulted in lower levels of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), caspase-3, and transforming growth factor-beta (TGF-β) in the liver tissue homogenates. Liver function was more significantly improved by the drug-NP combination. Conclusions: This study verified the beneficial therapeutic effects of the combination of sildenafil and neem extract, particularly in NP forms, using biochemical, histological, and immunohistochemical analyses in a rat model of liver damage.

Rutin is a promising nutraceutical with potential antibacterial and prophylactic activities. This work aimed to evaluate the protective effect of Rutin nanovehicle, which were formulated as a mucoadhesive intranasal preparation, on mice experimentally challenged with Pasteurella multocida. The extracted Rutin nanoplatform was laden into different concentrations of mucoadhesive hydroxy propyl methyl cellulose (HPMC). The ex vivo permeability of Rutin nanoformulations across the nasal mucosa was evaluated. The optimal formulation was examined in vivo, and group 1 was not infected or prophylactic. Group 2 was infected with P. multocida-nonprotected, and groups 3 and 4 were prophylactic groups that were protected with free Rutin extract and Rutin nanoformulation, respectively, via the intranasal route. The bacterial count in vital organs was carried out post challenge with P. multocida to determine protective effect of free Rutin extract and Rutin nanoformulation, also pathological changes in the vital organs were examine, level of IgG was determined, Cytokines concentration; Interferon Gamma (INF-γ) and Interlukin-12 (IL -12) was assessment by using sandwich ELISA. The rutin nanoparticulate system containing the lowest amount of HPMC exhibited enhanced permeated amount (311.64± 10.0 μg/cm2) and steady state flux 6.67± 0.10 μg /cm 2/sec across nasal mucosa. The results of the in vivo study revealed that the rutin nanoformulation showed a significant reduction in the bacterial count, histopathological lesions in the examined organs. Also, increased the hormonal response of mice where it increased levels of antibodies IgGs and modulation in the concentration of serum IFN-γ and IL-12. The mucoadhesive intranasal Rutin nanovehicle has remarkable immunomodulatory effects and can be used for protection against Pasteurella multocida in animals.

Rosuvastatin (ROS), a statin drug with promising anticancer properties has a low bioavailability of approximately 20% due to lipophilicity and first-pass m

Purpose: Despite having a wide range of therapeutic advantages, dexamethasone (DEXM)-free formulations have some negative side effects that manifest over time. Polymeric nanocapsules (PNCs) exhibit a core-shell structure that can encapsulate and control the release of drug products. Accordingly, the present study aimed to develop a new nanoparticulate system, PNCs, as drug nanocarriers of DEXM and to exemplify the difference in safety profile regarding the gastropathic and cardiopathic effects of DEXM PNCs versus free DEXM. Methods: Dexamethasone-loaded alginate nanocapsules were prepared using the nanoprecipitation technique and evaluated for different parameters. In-vivo assessment of the safety profile of the DEXMs (free and PNCs) necessitated three animal groups: vehicle, free DEXM, and DEXM PNCs groups. Treatments with DEXM were administered intraperitoneally, once daily, for 7 days. Stomach and heart samples were investigated for tissue damage. Tissue insults were assessed via macroscopic, biochemical, histopathological, and immunohistochemical analyses. Results: The selected PNCs exhibited a small particle size of 287 ± 7.5 nm, a zeta-potential of -21.06 ± 0.23 mV, an encapsulation efficiency of 91.53 ± 0.5%, and a prolonged release profile for up to 48 h as compared with a free drug. Gastric damage indicators showed more serious mucosal damage with free DEXM, hemorrhagic ulcers, and enhanced oxidative stress than the DEXM PNCs. Biomarkers of cardiac damage were significantly elevated with free DEXM and significantly lower in the DEXM PNCs group. Conclusion: Dexamethasone was successfully encapsulated into polymeric nanocapsules of sodium alginate coating polymer. The developed alginate nanocapsules exhibited desirable parameters and a superior anticipated side effect profile regarding gastric and cardiac damage.

Curcumin (CR) is a natural product that has great interest in biopharmaceutical applications. It has several biological effects that antagonizes inflammation, oxidative stress, and cancer. On the other hand, low aqueous solubility, stability, and dissolution rate are the main challenges to using curcumin. In the present investigation, curcumin was formulated as a nanosystem known as nanocurcumin using a combination of polyvinyl pyrrolidone (PVP) with different polymers as stabilizing agents. The nanocurcumin formulations were prepared and evaluated by measuring the particle size, surface charge, drug content, and stability. The selected nanocurcumin formulation prepared using PVPK30-Poloxamer 188 demonstrated a significantly smaller particle size (272.1 ± 15.32 nm) and a higher settlement volume ration as compared with other formulations. Also, the selected formulation showed higher solubility and dissolution rates as compared with other stabilizer combinations. Chitosan was added to the selected nanocurcumin formulation as a coating polymer to enhance short-term storage colloidal stability. The result of stability proved that chitosan (0.05%)-coated nanocurcumin dispersion showed good stability during storage as compared with non-coated nanocurcumin. Non-coated nanocurcumin and chitosan-coated curcumin were loaded into the Carbopol934 hydrogel matrix to investigate the effect on curcumin permeability across the skin. The results revealed that nanocurcumin hydrogel formulations showed a significantly higher amount of curcumin permeated across the skin.