Background Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro . Objective We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. Methods 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. Results 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). Conclusion 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. Clinicaltrials.gov Identifier NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569 .

These results confirm the potential of these mucoadhesive vaginal tablets to enhance P4 efficacy and avoid the side effects associated with IM injection.

Curcumin (CUR) is one of the most commonly used herbal product; it shows effective antiinflammatory and anti-oxidant effects. However, poor aqueous solubility and low permeability are the major challenges in therapeutic application of curcumin. One class of vesicular nanocarriers called "Niosome and ethosome" which have proved to possess distinct advantages were used to encapsulate curcumin and evaluated for their morphology, particle size, zeta potential, entrapment efficiency (EE%) and drug release. They were incorporated into hydroxy propyl methyl cellulose (HPMC15000) gel then, evaluated on the rat skin via inhibition of carrageenan induced rat paw edema. The results showed that the particle size of curcumin loaded niosomes and ethosomes were ranged (317.5±1.91 to 558.3±8.587 nm) and (182.1±5.3 to 354.5±30.03 nm), respectively. Skin permeation studies demonstrated that CUR permeability coefficient through rat kin for gel formulations of loaded vesicles was ~ four times higher as compared to free CUR. The in-vivo anti-inflammatory studies proved that gel formulations of CUR vesicles possessed higher significant inhibition of carrageenan induced rat paw edema when compared to pure curcumin. Accordingly, the results revealed that, curcumin loaded nanovesicels held great potential approaches as anti-inflammatory in topical application.

These results confirm that Brij®35 and Pluronic® F-127 micelles are promising carriers to overcome PG shortcomings through enhancing its aqueous solubility and vaginal permeability.

A new formulation (niosomes) was prepared to enhance the bioavailability, hepatic tissue uptake, and hepatoprotective activity of glutathione (GSH). The GSH-loaded niosomes (nanoform, N-GSH) were formulated by the thin-film hydration technique using cholesterol/non-ionic surfactants (Span®40, Span®60, and Tween®80) at a componential ratio of 1:1 and 2:1. The hepatoprotective activity of N-GSH, GSH, and the standard silymarin against CCl4-induced liver damage and oxidative stress were tested on the rats’ model. The hepatic morphology and histopathological characters were also investigated. The tissue contents of N-GSH were analysed using a concurrently validated RP-HPLC method. The optimized niosomes, composed of glutathione (500 mg), cholesterol, and Span®60-Tween®80 at a molar ratio of 2:1 of cholesterol/non-ionic surfactant, displaying a particle size of 688.5 ± 14.52 nm, a zeta potential of −26.47 ± 0.158 mV, and encapsulation efficiency (EE) of 66 ± 2.8% was selected for in vivo testing. The levels of MDA, NO, SOD, NF-κB, IL-1β, and Bcl-2 were measured. The results demonstrated that hepatic tissue damage was ameliorated using N-GSH as confirmed by the morphological and histopathological examination compared to the CCl4 and control groups. The N-GSH significantly (p < 0.05) decreased the elevated levels of hepatic enzymes, oxidative parameters, and inflammatory mediators, as compared to silymarin and GSH. Also, N-GSH significantly (p < 0.05) increased GSH hepatocyte concentrations as compared to the control groups. The present study demonstrated that N-GSH remarkably improved glutathione oral bioavailability and hepatic tissue uptake, thereby introducing a new glutathione formulation to protect hepatic tissue from injury and restore its GSH contents.

Curcumin (CUR) is a nature polyphenolic phytoingredient. CUR showed anti-inflammatory, anti-oxidant, anti-fungal and anticancer activities. The therapeutic efficacy of CUR was limited due to its poor aqueous solubility, poor oral bioavailability. Poor solubility of drugs is the major challenge associated with formulation development. Therefore, the aim of present work was to enhance CUR aqueous solubility and dissolution rate using Physical mixture and its solid dispersion. CUR solid dispersions were prepared by solvent evaporation and Freeze drying techniques using different polymers, such as β-cyclodextrins, polyvinyl pyrrolidone (PVP K30), polyethylene glycol 6000 and Pluronic ® F-127. The prepared physical mixtures, solid dispersions were characterized using different techniques such as (DSC), (FTIR) and (XRD). Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The results of physical characterization of the different systems show no interaction between them. Dissolution studies of CUR solid dispersions showed that the highest drug dissolution rate was achieved at CUR/ Pluronic®F-127 weight ratio of 1:3. Also, complete drug dissolution was obtained for CUR/Pluronic F-127 solid dispersion after 30 min compared to 35 % dissolution for CUR alone after the same time. Also, CUR permeability coefficient through rat skin for Pluronic®F-127 micelles and solid dispersion were two times higher than that of the CUR alone. The obtained results concluded that, the preparation of solid dispersion of Pluronic®F-127 solid dispersions by freeze drying method is a promising one to overcome CUR shortcomings through enhancing its aqueous solubility, dissolution rate and skin permeability.

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.

Purpose Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia. Methods It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group “ivermectin group” included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients “placebo group” who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done. Results The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05. Conclusion In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment. Trial Registration No NCT04951362.