This study aims to develop efficient topical therapy for keratomycosis using sertaconazolenitrate (STZN)-loaded leciplex (LP). The D-optimal design was used to optimize STZN-loaded LP by utilizing soy phosphatidylcholine (SPC) molar ratio (X₁), cationic surfactant molar ratio (X₂), and cationic surfactant type (X₃) as the independent variables, whereas their impact was studied for entrapment efficiency percent (EE; Y₁), particle size (PS; Y₂), polydispersity index (PDI; Y₃), zeta potential (ZP; Y₄), and permeability coefficient (Kp; Y₅). The optimized formula was evaluated regarding morphology, ex vivo permeation, mucoadhesion, stability, and in vivo studies. The optimized formula was spherical and showed EE of 84.87 ± 1.71%, PS of 39.70 ± 1.35 nm, PDI of 0.242 ± 0.006, ZP of +54.60 ± 0.24 mV, and Kp of 0.0577 ± 0.0001 cm/h. The ex vivo permeation study revealed that the optimized formula enhanced the Kp and corneal deposition by 2.78 and 12.49 folds, respectively, compared to the aqueous drug dispersion. Furthermore, the optimized formula was stable and revealed promising mucoadhesion properties. Finally, the in vivo studies showed that the optimized formula was superior to the drug dispersion in treating rats with induced keratomycosis. These results confirmed the capabilities of LP as a promising nanocarrier for treating ocular diseases topically.

Objectives: This study was designed to optimize a ceftazidime (CTZ)-loaded nanocarrier that could efficiently permeate across corneal tissues. Moreover, N-acetylcysteine (NAC) was combined with an optimized CTZ-loaded formula to augment the antimicrobial activity and facilitate the efficient healing of Pseudomonas aeruginosa-induced keratitis. Methods: Different CTZ-loaded invasomes (INVs) and CTZ-loaded nanostructured lipid carriers (NLC) were fabricated and fully characterized via the determination of the entrapment efficiency (EE%), particle size (PS), surface charge, and percentage of CTZ release. Next, NAC was added to the optimized formulae from each nanocarrier, which were further assessed through ex vivo corneal permeation and in vitro antimicrobial activity studies. Finally, an in vivo evaluation of the optimal nanocarrier in the presence of NAC was performed. Results: Both nanocarriers showed nanoscale PS with sufficient surface charges. CTZ-loaded NLC formulae showed a higher EE% range with a sustained drug release profile. Both optimized formulae showed a spherical shape and excellent stability. Moreover, the antibacterial activity and biofilm inhibition assessments confirmed the synergistic effects of NAC when combined with different CTZ-loaded nanocarriers. However, the optimized CTZ-loaded INV formula achieved higher corneal permeation and deposition compared to the optimized CTZ-loaded NLC formula. Finally, the in vivo assessment confirmed the dominance of the optimized CTZ-loaded INV formula combined with NAC, where the microbiological, histopathological, and immunohistopathological examinations showed the rapid eradication of keratitis. Conclusions: Recent strategies for the incorporation of antibiotics into nanocarriers, combined with mucolytic agents, can offer a promising platform to boost the therapeutic efficiency of antibiotics and prevent antimicrobial resistance.

The present study reported leciplex (LPX) preparation using a simple mixing technique for 10 mL to 200 mL volumes. A D-optimal design was employed to study the effect of different variables on the characteristics of LPX and compare their impact where the batch volume (X1), mixing speed (X2), and mixing time (X3) were set as the independent variables, whereas their impact was studied for, particle size (PS; Y1), polydispersity index (PDI; Y2), zeta potential (ZP; Y3). Furthermore, the LPX batch prepared via optimized parameters was characterized for morphology by transmission electronic microscopy (TEM) and stability study. The PS (Y1) of different LPX batches were significantly affected by mixing speed (X2), while the PDI (Y2) and ZP (Y3) were influenced considerably by both mixing speed (X2) and mixing time (X3). The batch volume (X1) did not affect the characteristics of the prepared batches. The morphology of LPX was spherical and well dispersed. Furthermore, the optimized LPX batch was stable for 90 days of storage. Finally, it was shown that this fabrication method was appropriate for preparing LPX with good reproducibility and stability.