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Background/Objectives: Keratitis is an ocular disease caused by microbial infection or by non-infectious damage due to UV light exposure, chemical exposure, or eye injuries. Methods: Moxifloxacin-loaded ufasomes (MOX-UFAs) were optimized using a full factorial design (12.23) after being prepared by the vortex mixing method. The study evaluated the effects of the oleic acid amount, surface active agent (SAA) amount, and SAA type as independent factors on the entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount released after 6 h (Q6h%). Results: The optimized ufasomes (UFAs) formulation was spherical, with an EE% of 78.37 ± 3.91%, PS of 203.13 ± 20.31 nm, PDI of 0.334 ± 0.016, and ZP of −25.42 ± 1.27 mV. The in vitro release of moxifloxacin (MOX) from the UFAs was maintained for more than 6 h in the range of 40.0–75.0%. The optimum MOX-UFAs formulation was incorporated into an in situ gel (Pluronic F-127/HPMC K4M). The ex vivo studies (corneal permeation and confocal laser scanning microscopy) proved the successful retention of the MOX-UFAs-laden in situ gel. Furthermore, the in vitro and in vivo antimicrobial studies revealed their significant antimicrobial effect against Pseudomonas aeruginosa. In addition, the Draize test proved the tolerability of MOX-UFAs-laden in situ gel in animals. Conclusions: The incorporation of MOX-UFAs into Pluronic F-127/HPMC K4M in situ gel could successfully provide sustained ocular delivery and improve the bioavailability of MOX for the management of keratitis.

The present study deals with the formulation of topical insulin for wound healing with extended stability and sustained release, by applying quality by design concepts. Insulin has been promoted as a promising therapeutic wound healing agent. Topical formulation of insulin faced major problems, as it cannot be delivered safely to the wound with a controlled rate. Formulation of insulin-loaded vesicles in optimized bio-adhesive hydrogels has been explored to ensure a safe delivery of insulin to wounds in a controlled manner. Quality by design (QbD) was applied to study the effect of several critical process parameters on the critical quality attributes. Ishikawa diagram was used to identify the highest risk factors, which were screened by a fractional factorial design and augmented by Box–Behnken design. The optimized formula was incorporated into a mucoadhesive gel, which was further subjected to stability and clinical studies. An optimized formula was obtained with a particle size of 257.751 nm, zeta potential − 20.548 mv, 87.379% entrapment efficiency, and a release rate of 91.521 μg/cm2/h. The results showed that liposomal insulin remained stable for 6 months in aqueous dispersion state at 4°C. Moreover, the release was sustained up to 24 h. The clinical study showed an improvement in the wound healing rate, 16 times, as the control group, with magnificent reduction in the erythema of the ulcer and no signs of hypoglycemia. Insulin-loaded liposomal chitosan gel showed a promising drug delivery system with high stability and sustained release.

The pathogenesis of the coronavirus disease 2019 (COVID-19) involves a complex group of cytokines and is significantly influenced by genetic and epigenetic factors. The current study aims to assess the association of COVID-19 severity and mortality with the relative expression of MicroRNA-155 (miR-155) and its association with serum levels of interleukin (IL)-6, IL-10, and their derived ratio. This pilot case-control study included 75 COVID-19 patients and 25 healthy controls. Serum levels of cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA), and assessment of miR-155 relative expression level was done using quantitative real-time PCR in all participants. We found that IL-6, IL-10, IL-6/IL-10 ratio, and miR-155 expression levels were significantly higher in COVID-19 patients than in healthy controls ( p -values < 0.001). The expression level of miR-155 showed significant differences between all severity categories of COVID-19, reaching its highest levels in the severe group. It was also significantly higher in ICU-admitted patients ( p -value < 0.001) and those who died during their hospital stay ( p -value = 0.001). It showed a significant negative correlation with serum IL-10 ( r =-0.249, p -value = 0.031) and a significant positive correlation with IL-6/IL-10 ratio ( r  = 0.234, p -value = 0.043). It was also the only independent risk factor for COVID-19 severity by regression analysis and the best predictor for COVID-19 severity by ROC curve analysis. This study reported elevation of cytokines and miR-155 expression in COVID-19 patients. The level of miR-155 expression was associated with COVID-19 severity, mortality, and ICU admission, indicating its potential utility as a biomarker for monitoring the progression of COVID-19 and guiding patient follow-up.

Cell-free DNA (cfDNA) has emerged as a potential biomarker for assessing disease activity and prognosis in rheumatoid arthritis (RA). However, the association between cfDNA levels and the established RA markers of inflammation and disease severity remains unclear. The current study aimed to detect plasma levels of cfDNA in patients with RA and to investigate their association with RA activity indicators (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score-28 (DAS28)), prognostic markers (rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA)), and the musculoskeletal ultrasonographic (US7) scores. This controlled cross-sectional study included 108 RA patients and 108 healthy controls. Plasma levels of cfDNA were quantified by real-time PCR using ALU repeats. Levels of ESR, CRP, RF, and ACPA were measured using routine laboratory assays. Synovial inflammation and joint damage evaluation was performed using the US7 scoring system. Plasma levels of cfDNA were higher in RA patients than controls (P < 0.001) and significantly increased with higher DAS28 scores among all RA activity groups. Also, cfDNA levels were significantly positively correlated with ESR, CRP, RF, and ACPA levels (P-values <0.001). Regarding US7, cfDNA was significantly positively correlated with synovitis and erosion scores (P-values <0.05) but did not correlate significantly with tenosynovitis scores (P-values >0.05). In addition, plasma cfDNA was significantly higher in seropositive RA patients than in seronegative patients (P = 0.007). The odds ratio for cfDNA as a risk factor for erosions was 2.254. This study revealed that cfDNA levels are elevated in RA patients and positively associated with disease activity indicators and prognosis markers. Further research is warranted to validate these findings in larger cohorts and explore the clinical implications of cfDNA measurement in RA management.