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Although, approximately 30% of the world's population is estimated to be infected with Toxoplasma gondii (T. gondii) with serious manifestations in immunocompromised patients and pregnant females, the available treatment options for toxoplasmosis are limited with serious side effects. Therefore, it is of great importance to identify novel potent, well tolerated candidates for treatment of toxoplasmosis. The present study aimed to evaluate the effect of Zinc oxide nanoparticles (ZnO NPs) synthesized using Zingiber officinale against acute toxoplasmosis in experimentally infected mice. The ethanolic extract of ginger was used to prepare ZnO NPs. The produced ZnO NPs were characterized in terms of structure and morphology using Fourier Transformed Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), UV- spectroscopy and scanning electron microscopy (SEM). The prepared formula was used in treatment of T. gondii RH virulent strain. Forty animals were divided into four groups, with ten mice per group. The first group was the uninfected, control group. The second group was infected but untreated. The third and the fourth groups received ZnO NPs and Spiramycin orally in a dose of 10 mg/kg and 200 mg/kg/day respectively. The effect of the used formulas on the animals survival rate, parasite burden, liver enzymes -including Alanine transaminase (ALT) and aspartate transaminase (AST)-, nitric oxide (NO) and Catalase antioxidant enzyme (CAT) activity was measured. Moreover, the effect of treatment on histopathological alterations associated with toxoplasmosis was examined. Mice treated with ZnO NPs showed the longest survival time with significant reduction in the parasite load in the livers and peritoneal fluids of the same group. Moreover, ZnO NPs treatment was associated with a significant reduction in the level of liver enzymes (ALT, AST) and NO and a significant increase in the antioxidant activity of CAT enzyme. SEM examination of tachyzoites from the peritoneal fluid showed marked distortion of T. gondii tachyzoites isolated from mice treated with ZnO NPs in comparison to untreated group. T. gondii induced histopathological alterations in the liver and brain were reversed by ZnO NPs treatment with restoration of normal tissue morphology. The produced formula showed a good therapeutic potential in treatment of murine toxoplasmosis as demonstrated by prolonged survival rate, reduced parasite burden, improved T. gondii associated liver injury and histopathological alterations. Thus, we assume that the protective effect observed in the current research is attributed to the antioxidant capability of NPs. Based on the results obtained from the current work, we suggest greenly produced ZnO NPs as a chemotherapeutic agent with good therapeutic potential and high levels of safety in the treatment of toxoplasmosis.

Rutin is a polyphenolic flavonoid with an interestingly wide therapeutic spectrum. However, its clinical benefits are limited by its poor aqueous solubility and low bioavailability. In an attempt to overcome these limitations, rutin nanocrystals were prepared using various stabilizers including nonionic surfactants and nonionic polymers. The nanocrystals were evaluated for particle size, zeta potential, drug entrapment efficiency, morphology, colloidal stability, rutin photostability, dissolution rate, and saturation solubility. The selected nanocrystal formulation was dispersed in a hydrogel base and the drug release kinetics and permeability through mouse skin were characterized. Rutin’s anti-inflammatory efficacy was studied in a carrageenan-induced rat paw edema model. The nanocrystals had a size in the range of around 270–500 nm and a polydispersity index of around 0.3–0.5. Nanocrystals stabilized by hydroxypropyl beta-cyclodextrin (HP-β-CD) had the smallest particle size, highest drug entrapment efficiency, best colloidal stability, and highest drug photostability. Nanocrystals had around a 102- to 202-fold and 2.3- to 6.7-fold increase in the drug aqueous solubility and dissolution rate, respectively, depending on the type of stabilizer. HP-β-CD nanocrystals hydrogel had a significantly higher percent of drug released and permeated through the mouse skin compared with the free drug hydrogel. The cumulative drug amount permeated through the skin was 2.5-fold higher than that of the free drug hydrogel. In vivo studies showed that HP-β-CD-stabilized rutin nanocrystals hydrogel had significantly higher edema inhibition compared with the free drug hydrogel and commercial diclofenac sodium gel. These results highlight the potential of HP-β-CD-stabilized nanocrystals as a promising approach to enhance drug solubility, dissolution rate, and anti-inflammatory properties.

This study assessed the clinical effectiveness of orange peel polymethoxy-flavonoids rich fraction (OPMF) solid dispersion as a palatal dressing material, compared with Alveogyl, in a randomized clinical trial. After harvesting free gingival grafts for 18 patients in three groups, the donor site in group I received OPMF; group II received Alveogyl; and group III received placebo dough material. The visual analog scale (VAS) pain score in group I showed the lowest value in week one without a significant difference. In week 2, there was a substantial decrease in pain in group I compared to group III. Week 4 showed reduced pain scores in all groups without significant differences. The results of the number of analgesic pills revealed, after 1 week, the lowest number of pills consumed in group I, with a considerable difference compared to group III. Healing process results showed that group I had the highest healing values in each interval, with a significant difference between group I and group III at 1 and 2 weeks. Color matching parameter showed slight differences between the groups’ readings in favor of group I in all intervals without a statistically significant difference. The results suggest OPMF as a palatal dressing material that facilitates hemostasis, pain relief, and palatal wound healing.

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, −38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1β, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.

Acute renal failure (ARF) is a sudden, significant, and often reversible decline in kidney function, with 25% of all hospital-administered pharmaceuticals potentially causing nephrotoxicity. The study investigates the effectiveness of a novel nanoparticle (NP) formulation of glutathione (GSH) and Lepidium sativum (LS) in improving therapeutic outcomes in a rat model of ARF. Sixty adult male albino rats were allocated into ten groups, comprising six rats each, for the study. ARF was created by daily gentamicin (GN) administration for seven consecutive days and various treatment protocols, including chitosan (CS) NPs, spanlastics NPs, as well as conventional, NP formulations of GSH, LS, and their respective combinations. The effect was evaluated through various tests, and properties of nanoparticles were confirmed through characterization processes. The NP compositions markedly enhanced renal function, as seen by reduced urine concentrations of albumin and glucose. Furthermore, the serum concentrations of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C were decreased. Tissue concentrations of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA), as markers of oxidative stress, were enhanced by both conventional and NP formulations. Additionally, they decreased inflammatory markers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Histological analysis and immunohistochemical testing revealed that the combination therapy, particularly with the nanoforms, significantly decreased caspase 3 cellular immunoexpression, a sign of kidney cellular damage. The findings show that the ARF renal damage is considerably reduced when NPs containing GSH and LS are administered together. The study suggests a promising pharmacological approach for enhancing kidney regeneration and preserving renal function, potentially aiding in new therapeutic interventions for ARF treatment.

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.

Ginger extract (GE) has sparked great interest due to its numerous biological benefits. However, it suffers from limited skin permeability, which challenges its transdermal application. The target of the current work was to develop transethosomes as a potential nanovehicle to achieve enhanced transdermal delivery of GE through the skin. GE-loaded transethosomes were prepared by cold injection using different edge activators. The fabricated nanovesicles were evaluated for particle size, ζ-potential, encapsulation efficiency, and in vitro drug release. The selected formulation was then laden into the hydrogel system and evaluated for ex vivo permeability and in vivo anti-inflammatory activity in a carrageenan-induced rat-paw edema model. The selected formulation comprised of sodium deoxycholate exhibited particle size of 188.3±7.66 nm, ζ-potential of -38.6±0.08 mV, and encapsulation efficiency of 91.0%±0.24%. The developed transethosomal hydrogel containing hydroxypropyl methylcellulose was homogeneous, pseudoplastic, and demonstrated sustained drug release. Furthermore, it exhibited improved flux (12.61±0.45 μg.cm /second), apparent skin permeability (2.43±0.008×10 cm/second), and skin deposition compared to free GE hydrogel. In vivo testing and histopathological examination revealed that the GE transethosomal hydrogel exhibited significant inhibition of edema swelling compared to free GE hydrogel and ketoprofen gel. The animals that were treated with ginger transethosome hydrogel showed a significant decrement in reactive oxygen species and prostaglandin E compared to untreated animals. Transethosomes might be a promising new vehicle for GE for effective skin permeation and anti-inflammation. To the best of our knowledge, this work is the first utilization of transethosomes laden into hydrogel as a novel transdermal delivery system of GE.

Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication . We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.

Rosuvastatin (ROS), a statin drug with promising anticancer properties has a low bioavailability of approximately 20% due to lipophilicity and first-pass metabolism. This study aimed to enhance ROS anticancer efficacy through loading into flexible chitosomes. The chitosomes were prepared starting from negatively charged liposomes through electrostatic interactions with chitosan. The conversion of zeta potential from negative to positive confirmed the successful formation of chitosomes. The chitosan coating increased the particle size and zeta potential, which ranged from 202.0 ± 1.7 nm to 504.7 ± 25.0 nm and from − 44.9 ± 3.0 mV to 50.1 ± 2.6 mV, respectively. Chitosan and drug concentrations had an important influence on the chitosome properties. The optimum chitosome formulation was used to prepare ROS-loaded flexible chitosomes using different concentrations of four edge activators. The type and concentration of edge activator influenced the particle size, drug entrapment efficiency, and drug release rate of the flexible chitosomes. Flexible chitosomes significantly increased drug permeation through rat abdominal skin compared to control transferosomes and drug solution. The optimal ROS flexible chitosomes containing sodium deoxycholate as an edge activator had a 2.23-fold increase in ROS cytotoxic efficacy against MCF7 cells and a 1.84-fold increase against HepG2 cells. These results underscore the potential of flexible chitosomes for enhancing ROS anticancer efficacy. Graphical Abstract

Purpose: Immunomodulatory and broad-spectrum antiviral activities have motivated the evaluation of curcumin for Coronavirus infection 2019 (COVID-19) management. Inadequate bioavailability is the main impediment to the therapeutic effects of oral Cur. This study aimed to develop an optimal curcumin transferosome-loaded thermosensitive in situ gel to improve its delivery to the lungs. Methods: Transferosomes were developed by using 33 screening layouts. The phospholipid concentration as well as the concentration and type of surfactant were considered independent variables. The entrapment efficiency (EE%), size, surface charge, and polydispersity index (PDI) were regarded as dependent factors. A cold technique was employed to develop thermosensitive in-situ gels. Optimized transferosomes were loaded onto the selected gels. The produced gel was assessed based on shape attributes, ex vivo permeability enhancement, and the safety of the nasal mucosa. The in vitro cytotoxicity, antiviral cytopathic effect, and plaque assay (CV/CPE/Plaque activity), and in vivo performance were evaluated after intranasal administration in experimental rabbits. Results: The optimized preparation displayed a particle size of 664.3 [+ or -] 69.3 nm, EE% of 82.8 [+ or -] 0.02%, ZP of -11.23 [+ or -] 2.5 mV, and PDI of 0.6 [+ or -] 0.03. The in vitro curcumin release from the optimized transferosomal gel was markedly improved compared with that of the free drug-loaded gel. An ex vivo permeation study revealed a significant improvement (2.58-fold) in drug permeability across nasal tissues of sheep. Histopathological screening confirmed the safety of these preparations. This formulation showed high antiviral activity against SARS-CoV-2 at reduced concentrations. High relative bioavailability (226.45%) was attained after the formula intranasally administered to rabbits compared to the free drug in-situ gel. The curcumin transferosome gel displayed a relatively high lung accumulation after intranasal administration. Conclusion: This study provides a promising formulation for the antiviral treatment of COVID-19 patients, which can be evaluated further in preclinical and clinical studies. Keywords: transferosomes, curcumin, in situ gels, coronavirus 2, SARS-CoV-2, intranasal delivery