Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at developing novel modified spanlastics by modulating spanlastics composition using different glycols for enhancing TOL ocular delivery. To achieve this goal, TOL basic spanlastics were prepared by ethanol injection method using a full 3² factorial design. By applying the desirability function, the optimal formula (BS6) was selected and used as a nucleus for preparing and optimizing TOL-cosolvent spanlastics according to the full 3¹.2¹ factorial design. The optimal formula (MS6) was prepared using 30% propylene glycol and showed entrapment efficiency percent (EE%) of 66.10 ± 0.57%, particle size (PS) of 231.20 ± 0.141 nm, and zeta potential (ZP) of −32.15 ± 0.07 mV. MS6 was compared to BS6 and both nanovesicles significantly increased the corneal permeation potential of TOL than drug suspension. Additionally, in vivo histopathological experiment was accomplished and confirmed the tolerability of MS6 for ocular use. The fungal susceptibility testing using Aspergillus niger confirmed that MS6 displayed more durable growth inhibition than drug suspension. Therefore, MS6 can be a promising option for enhanced TOL ocular delivery.

Neonatal sepsis is a life-threatening condition and Staphylococcus aureus is one of its major causes. However, to date, no rapid and sensitive diagnostic tool has been developed for its direct detection. Bioinformatics analyses identified a surface-exposed 112-amino acid polypeptide of the cell wall protein NWMN_1649, a surface protein involved in cell aggregation and biofilm formation, as being a species-specific and highly conserved moiety. The polypeptide was cloned, purified, and used to immunize mice to raise specific immunoglobulins. The purified antibodies were conjugated to gold nano-particles and used to assemble an immunochromatographic strip (ICS). The developed prototype ICS detected as low as 5 µg purified polypeptide and 10² CFU/mL S. aureus within 15 min. The strip showed superior ability to directly detect S. aureus in neonatal sepsis blood specimens without prior sample processing. Moreover, it showed no cross-reaction in specimens infected with two other major causes of neonatal sepsis; coagulase-negative staphylococci and Klebsiella pneumoniae. The selected NWMN_1649-derived polypeptide demonstrates success as a promising biomolecule upon which a prototype ICS has been developed. This ICS provides a rapid, direct, sensitive, and specific option for the detection of S. aureus causing neonatal sepsis. Such a tool is urgently needed especially in resources-limited countries.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections which, due to the spread of antimicrobial resistance, have become increasingly serious. Bacterial skin infection affects the barrier function of skin causing depletion of the ceramide content in the stratum corneum (SC) of the epidermis. In the study reported herein, luteolin (LUT) a naturally-occurring flavonoid was incorporated in PEGylated cerosomes (PCs) to boost its antibacterial action as a topical application. The opimal formulation of the surface-modified lipidic vesicles was chosen with the aid of a 2³ full factorial design. The effectiveness of the optimal LUT formulation which was developed was evaluated using several MRSA strains both in vitro and in vivo studies. Results: A 2³ full factorial design was employed for the preparation of the optimum PC formulation, designated herein as F5. A comparative in vitro release study revealed the superiority of F5 over a LUT suspension in solubilizing and releasing after 24 h, a higher percentage 78.1 ± 1.8% of luteolin compared with only 18.3 ± 2.1% for the luteolin suspension. When tested against MRSA strains, F5 showed antimicrobial activity that was higher than that of the luteolin suspension, having a MIC value of 187.5 µg/mL versus 1500 µg/mL. In addition to having enhanced anti-virulence activity than the luteolin suspension in terms of antibiofilm formation (with % inhibition ranging from 45 to 99% with the tested strains at 0.5 × and 0.25 × MICs, where the luteolin suspension only had a range from 1 to 45%), enhanced anti-pigment production, and anti-α-hemolysin activity were also observed. Moreover, F5 affected the cell wall integrity as confirmed by transmission electron microscopy (TEM). Scanning electron microscopy (SEM) verified the effect of F5 on bacterial biofilm formation, showing reduction of cellular adhesion and disruption of biofilm, factors which greatly contribute to bacterial pathogenesis and antibiotic resistance. When compared to the negative control and the luteolin suspension groups, the F5 formulation also resulted in reducing the bacterial load in the murine skin infection model. Conclusions: F5 PEGylated cerosomes are potential new potent defense agents against MRSA infections, demonstrating promising therapeutic capabilities.

Chronic infected wounds with multi-drug resistant pathogens present severe therapeutic challenges, often leading to prolonged morbidity and impaired healing. To address this, we engineered a multifunctional wound dressing by integrating Voriconazole-loaded silver/zinc MOFs (VOR@Ag/Zn-MOFs) into a hyaluronic acid/polyvinylpyrrolidone (HA/PVP) matrix. The composite was prepared through sequential steps, including preparing a HA/PVP polymer blend via solvent dissolution, synthesizing bimetallic Ag/Zn-MOFs through chemical precipitation, loading VOR into MOF nanocages, and consolidating the composite via chemical crosslinking followed by freeze-drying. Comprehensive physicochemical characterization to confirm MOF stability was implemented through SEM/EDX, confirming uniform nanocage architecture and elemental distribution (Ag/Zn/F), while DLS revealed controlled particle dimensions, and optimal colloidal stability (PDI 0.694; ZP + 39.3 mV). FTIR confirmed structural integrity through preserved polymer peaks (O–H 3400–3200, C = O 1650 cm⁻1), VOR-specific C-F (1400–1200 cm⁻1), and MOF Zn–O bonds (1100–1000/400–600 cm⁻1), verifying non-covalent integration without degradation. XRD further verified the crystalline framework integrity. In-vitro release studies demonstrated sustained biphasic release (44.2% ± 5.9 burst within 6 h; up to 77.1% ± 1.8 controlled release over 360 h). The composite demonstrated exceptional antimicrobial synergy, including potent antifungal activity against Candida albicans  (MFC 1.4 µg/mL, 214-fold lower than free VOR) with microscopically-confirmed cell wall disruption, and broad bacteriostatic activity (MIC range 8,500–17,000 µg/mL against Gram-positive and Gram-negative pathogens). Critically, it achieved complete fungal clearance within 24 h. Simultaneously, it accelerated tissue regeneration, showing outstanding fibroblast biocompatibility (IC₃₀ > 3,000 µg/mL; 6,000-fold safety margin) and enabling marked wound closure within 72 h in the wound healing study. By converging triple-action mechanisms, including metal ion synergy (Ag⁺/Zn2⁺), targeted azole delivery, and HA/PVP-mediated pro-regenerative signaling, this platform uniquely eliminates resilient infections and restores wound integrity that was previously unattainable with conventional azole therapies. Graphical Abstract