The Development and Characterization of a Next-Generation Oncolytic Virus Armed with an Anti-PD-1 sdAb for Osteosarcoma Treatment In Vitro.

Osteosarcoma (OS) is a primary bone malignancy characterized by an aggressive nature, limited treatment options, low survival rate, and poor patient prognosis. Conditionally replicative adenoviruses (CRAds) armed with immune checkpoint inhibitors hold great potential for enhanced therapeutic efficacy. The present study aims to investigate the anti-tumor efficacy of CAV2-AU-M2, a CAV2-based CRAd armed with an anti-PD-1 single-domain antibody (sdAb), against OS cell lines in vitro. The infection, conditional replication, cytopathic effects, and cytotoxicity of CAV2-AU-M2 were tested in four different OS cell lines in two-dimensional (2D) and three-dimensional (3D) cell cultures. CAV2-AU-M2 showed selective replication in the OS cells and induced efficient tumor cell lysis and death. Moreover, CAV2-AU-M2 produced an anti-PD-1 sdAb that demonstrated effective binding to the PD-1 receptors. This study demonstrated the first CRAd armed with an anti-PD-1 sdAb. This combined approach of two distinct immunotherapies is intended to enhance the anti-tumor immune response in the tumor microenvironment.

A triple combination of latanoprost, fractional CO2 laser, and platelet-rich plasma in localized vitiligo: A clinical and histopathologic study.

BACKGROUND: Several treatment modalities are available for the treatment of vitiligo due to the lack of a uniformly effective therapy. Topical latanoprost 0.005% is an effective topical treatment. Fractional CO2 laser alone or combined with platelet-rich plasma (PRP) has been proposed as effective adjunctive therapies. OBJECTIVES: We aimed to compare the efficacy of topical latanoprost 0.005% (Ioprost®, Orchidia, Egypt) combined with either add-on fractional CO2 laser or fractional CO2 -PRP versus topical latanoprost monotherapy in the treatment of localized stable vitiligo. PATIENTS/METHODS: The study included 60 patients randomly assigned into three equal groups. Group A patients received topical latanoprost drops only. Group B patients received topical latanoprost drops and fractional CO2 laser sessions at 2-week interval for 3 months. Group C patients received topical latanoprost drops and fractional CO2 laser sessions combined with PRP at a 2-week interval for 3 months. The mean improvement score by the physician was calculated 4 months after the start of the study. Punch skin biopsies were obtained before treatment and 4 months from the beginning of the study and stained with H&E and HMB-45 antibody for evaluation of pigmentation. RESULTS: Significant clinical improvement of vitiligo lesions with significant increase of re-pigmentation were reported in the three treated groups. Latanoprost in combination with fractional CO2 and PRP was associated with more significant therapeutic outcomes than either combined latanoprost and fractional CO2 or latanoprost alone. CONCLUSION: Fractional CO2 laser-PRP enhances the therapeutic efficacy of latanoprost 0.005% in the treatment of localized stable vitiligo.

An Innovative Approach for Formulation of Rutin Tablets Targeted for Colon Cancer Treatment.

The aim of this study was the improvement of rutin solubility along with targeting its release to colon for effective treatment of colon cancer. Five formulations of compression-coated tablets were prepared with the same core composition including rutin-polyvinyl pyrrolidone K30 solid dispersion (rutin-PVP K30 SD) but differ in being coated with either frankincense alone or different combinations of frankincense with gelatin. The superior formula was selected based on the in vitro drug release then further evaluated in terms of physical properties and in vivo performance in dogs using X-ray. Moreover, in vitro cytotoxicity of rutin, rutin-PVP K30 SD, frankincense, and a mixture of rutin-PVP K30 SD with frankincense in a ratio representing their concentrations in the selected formula was assessed against human colon cancer (HCT-116) cell lines using sulforhodamine B assay. The formula (F4) with the coat consisted of 65%w/w frankincense and 35%w/w gelatin achieved acceptable in vitro controlled drug release. In vivo X-ray in dogs confirmed that F4 tablet could remain intact in the stomach and small intestine until reaching the colon. In vitro cytotoxicity revealed that mixture of rutin-PVP K30 SD with frankincense was more effective in arresting cancer cell growth than rutin or frankincense alone. Moreover, stability studies revealed that F4 tablets were physically and chemically stable. Thus, improving rutin solubility using solid dispersion technique and formulating it into frankincense-based compression-coated (F4) tablets would be a successful approach for colonic delivery of rutin with potential of improving therapeutic efficacy.

Helicobacter pylori eradication rates using clarithromycin and levofloxacin-based regimens in patients with previous COVID-19 treatment: a randomized clinical trial.

BACKGROUND: Helicobacter pylori (H. pylori) is affecting half of the globe. It is considered a main causative organism of chronic gastritis, peptic ulcer disease, and different gastric maliganacies. It has been also correlated to extraintestinal diseases, including refractory iron deficiency anaemia, vitamin B12 deficiency, and immune thrombocytopenic purpura. The misuse of antibiotics during the coronavirus diseases 2019 (COVID-19) pandemic time can affect H. pylori eradication rates. Our aim was to compare the efficacy of clarithromycin versus levofloxacin-based regimens for H. pylori treatment in naïve patients after the COVID-19 pandemic misuse of antibiotics. METHODS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were recruited. Patients were randomized to receive either clarithromycin, esomeprazole, and amoxicillin, or levofloxacin, esomeprazole, and amoxicillin. RESULTS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were included, 135 in each arm. In total, 19 patients in the clarithromycin group and 18 patients in the levofloxacin group stopped treatment after 2-4 days because of side effects or were lost for follow-up. Finally, 116 subjects in the clarithromycin group and 117 in the levofloxacin group were assessed. The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: group I, 55.56% and 64.66%; and Group II, 64.44% and 74.36% respectively (p = 0.11). CONCLUSION: As COVID-19 pandemic has moved forward fast, high resistance rates of H. pylori to both clarithromycin and levofloxacin were developed after less than two years from the start of the pandemic. Molecular & genetic testing is highly recommended to identify antimicrobial resistance patterns. Strategies to prevent antibiotic misuse in the treatment of COVID-19 are needed to prevent more antibiotic resistance. TRIAL REGISTRATION: The trial was registered on Clinicaltrials.gov NCT05035186. Date of registration is 2-09-2021.

Multidimensional Environmental Factors and Sleep Health for Aging Adults: A Focused Narrative Review.

The timing, amount, and quality of sleep are critical for an individual's health and quality of life. This paper provides a focused narrative review of the existing literature around multidimensional environments and sleep health for aging adults. Five electronic databases, Scopus, Web of Science, PubMed/Medline; EBSCOhost, PsycINFO (ProQuest), and Google Scholar yielded 54,502 total records. After removing duplicates, non-peer reviewed academic articles, and nonrelevant articles, 70 were included for review. We were able to categorize environmental factors into housing security, home environment, and neighborhood environment, and, within each environmental category, specific elements/aspects are discussed. This paper provides a comprehensive map connecting identified levels of influence (individual, home/house, and neighborhood-level) in which subfactors are listed under each level of influence/category with the related literature list. Our review highlights that multidimensional environmental factors can affect aging adults' sleep health and eventually their physical, mental, and cognitive health and that sleep disparities exist in racial minorities in socioeconomically disadvantaged communities in which cumulative environmental stressors coexist. Based on this focused narrative review on the multidimensional sleep environments for aging adults, knowledge gaps are identified, and future research directions are suggested.

Investigating the Antibacterial Activity and Safety of Zinc Oxide Nanoparticles versus a Commercial Alcohol-Based Hand-Sanitizer: Can Zinc Oxide Nanoparticles Be Useful for Hand Sanitation?

Hand hygiene is the key factor to control and prevent the spread of infections, for example, hospital-acquired infections (HAIs). People commonly use alcohol-based hand sanitizers to assure hand hygiene. However, frequent use of alcohol-based hand sanitizers in a pandemic situation (e.g., COVID-19) was associated with serious drawbacks such as skin toxicity including irritation, skin dermatitis, and skin dryness or cracking, along with peeling, redness, or itching with higher possibility of infection. This demands the development of alternative novel products that are effective as alcohol-based hand sanitizers but have no hazardous effects. Zinc oxide nanoparticles (ZnO-NPs) are known to have broad-spectrum antimicrobial activity, be compatible with the biological system and the environment, and have applicable and economic industrial-scale production. Thus, ZnO-NPs might be a good candidate for hand sanitation. To the best of our knowledge, the antibacterial activity of ZnO-NPs in comparison to alcohol-based hand sanitizers has not yet been studied. In the present work, a comparative study of the antibacterial activity of ZnO-NPs vs. Sterillium, a commercial alcohol-based hand sanitizer that is commonly used in Egyptian hospitals, was performed against common microorganisms known to cause HAIs in Egypt, including Acinetobacter baumannii, Klebsiella pneumoniae, Methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus aureus. The safety profiles of ZnO-NPs and Sterillium were also assessed. The obtained results demonstrated the superior antibacterial activity and safety of ZnO-NPs compared to Sterillium. Therefore, ZnO-NPs could be a promising candidate for hand sanitation in comparison to alcohol-based hand sanitizers; however, several studies related to long-term toxicity and stability of ZnO-NPs and investigations into their antimicrobial activity and safety in healthcare settings are still required in the future to ascertain their antimicrobial activity and safety.

Development of a Novel Bilosomal System for Improved Oral Bioavailability of Sertraline Hydrochloride: Formulation Design, In Vitro Characterization, and Ex Vivo and In Vivo Studies.

This study was proposed to develop an optimized sertraline hydrochloride (SER)-loaded bilosomal system and evaluate its potential for enhancement of drug oral bioavailability. A full 23 factorial design was used to prepare SER-loaded bilosomal dispersions by thin film hydration using span 60, cholesterol (CHL), and sodium deoxycholate (SDC). The investigated factors included the total concentration of span 60 and CHL (X1), span 60:CHL molar ratio (X2), and SER:SDC molar ratio (X3). The studied responses were entrapment efficiency (EE%) (Y1), zeta potential (Y2), particle size (Y3), and in vitro % drug released at 2 (Y4), 8 (Y5), and 24 h (Y6). The selected optimal bilosomal dispersion (N1) composition was 0.5% w/v (X1), 1:1 (X2), and 1:2 (X3). Then, N1 was freeze dried into FDN1 that compared with pure SER for in vitro drug release, ex vivo permeation through rabbit intestine, and in vivo absorption in rats. Moreover, storage effect on FDN1 over 3 months was assessed. The optimal dispersion (N1) showed 68 ± 0.7% entrapment efficiency, - 41 ± 0.78 mV zeta potential, and 377 ± 19 nm particle size. The freeze-dried form (FDN1) showed less % drug released in simulated gastric fluids with remarkable sustained SER release up to 24 h compared to pure SER. Moreover, FDN1 showed good stability, fivefold enhancement in SER permeation through rabbit intestine, and 222% bioavailability enhancement in rats' in vivo absorption study compared to pure SER. The SER-loaded bilosomal system (FDN1) could improve SER oral bioavailability with minimization of gastrointestinal side effects.

In vitro and in vivo evaluation of cubosomal nanoparticles as an ocular delivery system for fluconazole in treatment of keratomycosis.

The objective of the present study was to enhance ocular antifungal activity of fluconazole (FCZ) in treatment of keratomycosis through incorporation into cubosomal nanoparticles. FCZ-loaded cubosomal dispersions were prepared by emulsification method according to 23 full factorial design. Design-Expert® software was used to study the effects of different formulation factors on properties of FCZ-loaded cubosomal dispersions and select the optimal formulation. Eight FCZ-loaded cubosomal dispersions were prepared and were in vitro and in vivo evaluated. In vitro, the results revealed that the optimum formula exhibited a mean particle size of 48.17 ± 0.65 nm and entrapped 85.70 ± 2.56% of FCZ. The ex vivo permeation study confirmed a two-fold enhancement in FCZ permeation through rabbit cornea compared to aqueous FCZ solution. Furthermore, in vivo ocular tolerance and histopathological studies proved the efficacy and safety FCZ-loaded cubosomal dispersion in treatment of induced keratomycosis in rats compared to aqueous FCZ solution after topical ocular application. In conclusion, the obtained results indicated that cubosomes could be promising ocular drug delivery system for enhancing antifungal activity of FCZ in treatment of fungal keratitis in rats. Graphical abstract.

Formulation and evaluation of cyclodextrin-based nanosponges of griseofulvin as pediatric oral liquid dosage form for enhancing bioavailability and masking bitter taste.

The aim of this study was the development of griseofulvin (GRI) loaded ß-cyclodextrin (ß-CD) based nanosponges for bitter taste masking, improving dissolution rate and oral bioavailability. Plain NS (NS1 NS2 and NS3) were fabricated by reacting ß-CD with the cross-linker diphenyl carbonate at different molar ratios (1:2, 1:4 and 1:6, respectively) using ultrasonication method. The NS2 provided both highest %yield and GRI solubilization enhancement. Thus, the drug was loaded in NS2 at different NS2: drug weight ratios in presence or absence of 0.25%w/w polyvinylpyrolidone (PVP k30). The GRI loaded NS (F1) that provided highest drug loading capacity and entrapment efficiency (47.20 ± 0.38%, 84.91 ± 0.30%, respectively) was morphologically examined using scanning electron microscopy (SEM). Also, Particle size, zeta potential, differential scanning calorimetry (DSC), Fourier transform infra-red (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, in-vitro release, taste masking potential were evaluated. Moreover, in-vivo Pharmacokinetic studies were performed on rats. The F1 showed particle size 665.9 ± 13.8 nm and zeta potential -21.5 ± 0.7 mV. The DSC and FT-IR analysis confirmed the complexation of GRI with NS2. Nanosponges (F1) provided 3.19, folds increase in dissolution efficiency %, 2.13 and 3.78 folds increase in Cmax and AUC0-48 compared to plain GRI. Taste masking evaluation confirmed the potential of GRI nanosponges (F1) in masking the bitter taste of GRI completely. The study confirmed that complexation of GRI with NS would be a viable approach for masking the bitter taste of GRI and improving oral bioavailability, that Cmax, Tmax and AUC 0-48 were significantly higher for the developed formulation (F1).

A systematic review of the safety and effectiveness of platelet-rich plasma (PRP) for skin aging.

Injection of platelet concentrates for the treatment of aging skin has gained popularity. The objective was to systematically assess the evidence regarding the safety and effectiveness of platelet-rich plasma (PRP) for reducing the visible signs of aging. Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus were searched from inception to March 2019 for prospective trials and case series assessing PRP for skin aging in 10 or more patients. Twenty-four studies, including 8 randomized controlled trials (RCTs), representing 480 total patients receiving PRP, were included. Based on physician global assessment, injection PRP monotherapy was shown to at least temporarily induce modest improvement in facial skin appearance, texture, and lines. Periorbital fine lines and pigmentation may also benefit. Adjuvant PRP accelerated healing after fractional laser resurfacing. Although the degree of improvement was typically less than 50%, patients generally reported high satisfaction. It was limited by heterogeneity in PRP preparation and administration, and lack of standardization in outcome measures. PRP injections are safe and may be modestly beneficial for aging skin. The evidence is most convincing for improvement of facial skin texture. The persistence of these effects is not known. More high-quality trials with sufficient follow-up are needed to optimize treatment regimens.

Protective Effects of Garlic and Cinnamon Oils on Hepatocellular Carcinoma in Albino Rats.

Natural oils are traditional medicinal herbs, which have attracted interests for its potential anti-inflammatory and anticancer activities. The present work is aimed at evaluating the protective effect of garlic oil and cinnamon oil on diethylnitrosamine- (DENA-) and 2-acetylaminofluorene- (2-AAF-) induced p53 gene mutation and hepatocarcinogenesis in rats. Forty male albino rats were divided into 4 equal groups: control, hepatocellular carcinoma (HCC), garlic oil-HCC, and cinnamon oil-HCC. The HCC-induced group showed a significant decrease in the body mass and a significant elevation in the liver weight, alpha-fetoprotein (AFP), liver enzymes, hepatic malondialdehyde (MDA), and p53 protein expression levels as well as genetic mutations in intron 5 of p53 gene in the form of Single-Nucleotide Polymorphisms (SNPs) and insertions. In addition, the glutathione (GSH) level and superoxide dismutase (SOD) activities were increased. While HCC rats pretreated with garlic oil or cinnamon oil were significantly reversed, these destructive actions increased GSH and SOD levels. The HCC-induced group showed histopathological features of liver cancer including hypercellularity, nuclear hyperchromasia, mitotic figures, and preneoplastic foci. On the other hand, HCC rats pretreated with garlic oil or cinnamon oil revealed partial reversal of normal liver architecture. The present findings proposed that these natural oils have the ability to improve liver function, significantly reduced the liver toxicity and HCC development. However, further sophisticated studies are recommended before their use as conventional therapeutics for HCC treatment.

Formulation and In Vitro and In Vivo Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration.

The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10 mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4 × 2(2) factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X 1), drug-lipid ratio (X 2), and filler type (X 3) on the percentage drug released at 8, 12, and 24 h (Y 1, Y 2, and Y 3) as dependent variables. Sixteen TBS sustained-release matrices (F1-F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug-Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24 h compared to immediate-release tablets.

Formulation, characterization, and clinical evaluation of microemulsion containing clotrimazole for topical delivery.

The objective of the present study was to formulate and evaluate microemulsion systems for topical delivery of clotrimazole (CTM). The solubility of CTM in various oils was determined to select the oil phase of the microemulsion systems. Pseudoternary phase diagrams were constructed to identify the area of microemulsion existence. Five CTM microemulsion formulations (M1-M5) were prepared and evaluated for their thermodynamic stability, pH, refractive index, droplet size, viscosity, and in vitro release across cellulose membrane. Among the prepared microemulsion formulations, M3 (lemon oil/Tween 80/n-butanol/water) and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were found to be promising according to their physical properties and CTM cumulative percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms for drug retention in the skin in comparison to the marketed CTM topical cream and their stability examined after storage at 40°C for 6 months. Microemulsion formulations achieved significantly higher skin retention for CTM over the CTM cream. Stability studies showed that M4 preparations were more stable than M3. The in vitro anti-fungal activity of M4 against Candida albicans was higher than that of the conventional cream. Moreover, clinical evaluation proved the efficacy and tolerability of this preparation in the treatment of various topical fungal infections.