Candida species is one of the pathogenic fungi of the eye responsible for keratitis that frequently causes vision impairment and blindness. Effective treatment requires long-term use of antifungal drugs, which is opposed by the defensive mechanisms of the eye and inadequate corneal penetration. The objective of this study was to develop a carrier for prolonged ocular application of fluconazole (FLZ) to treat keratitis. FLZ was encapsulated into chitosan fibrous matrices (F1–F4) using different chitosan concentrations (0.02, 0.1, 0.5, and 1%w/v, respectively) by freeze-drying as a single-step technique. Studying the morphology and surface properties of the inserts revealed a porous matrix with fibrous features with a large surface area. Thermal stability and chemical compatibility were confirmed by DSC/TGA/DTA and FT-IR, respectively. Loading capacity (LC) and entrapment efficiency (EE) were determined. According to the in vitro release study, F4 (0.11 mg mg⁻¹ LC and 87.53% EE) was selected as the optimum insert because it had the most sustained release, with 15.85% burst release followed by 75.62% release within 12 h. Ex vivo corneal permeation study revealed a 1.2-fold increase in FLZ permeation from F4 compared to FLZ aqueous solution. Also, in the in vivo pharmacokinetic study in rabbits, F4 increased the AUC_0-8 of FLZ by 9.3-fold and its concentration in aqueous humor was maintained above the MIC through the experimentation time. Studies on cytotoxicity (MTT assay) provide evidence for the safety and biocompatibility of F4. Therefore, the freeze-dried FLZ-loaded chitosan fibrous insert could be a promising candidate for treating ocular keratitis. Graphical Abstract

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.

Management of rheumatoid arthritis (RA) requires long-term administration of different medications since there has been no cure until now. Etodolac (ETD) is a nonsteroidal anti-inflammatory drug commonly used for RA management. However, its long-term administration resulted in severe side effects. This study aimed to develop a transdermal in situ gel incorporating ETD-loaded polymeric nanoparticles (NPs) to target the affected joints for long-term management of RA. Several PLGA NPs incorporating 1% ETD were prepared by nanoprecipitation and optimized according to the central composite design. The optimum NPs (F1) exhibited 96.19 ± 2.31% EE, 282.3 ± 0.62 nm PS, 0.383 ± 0.04 PDI, and −6.44 ± 1.69 ZP. A hyaluronate coating was applied to F1 (H-F1) to target activated macrophages at inflammation sites. H-F1 exhibited 287.4 ± 4.2 nm PS, 0.267 ± 0.02 PDI, and −23.7 ± 3.77 ZP. Pluronic F-127 in situ gel (H-F1G) showed complete gelation at 29 °C within 5 min. ETD permeation from H-F1G was sustained over 48 h when applied to microporated skin and exhibited significant enhancement of all permeation parameters. Topical application of H-F1G (equivalent to 8 mg ETD) to Wistarrat microporated skin every 48 h resulted in antirheumatic therapeutic efficacy comparable to commercial oral tablets (10 mg/kg/day).