Cationic Polyelectrolyte Nanocapsules of Moxifloxacin for Microbial Keratitis Therapy: Development, Characterization, and Pharmacodynamic Study.

Microbial keratitis (MK) is a vision-threatening disease and the fourth leading cause of blindness worldwide. In this work, we aim to develop moxifloxacin (MXN)-loaded chitosan-based cationic mucoadhesive polyelectrolyte nanocapsules (PENs) for the effective treatment of MK. PENs were formulated by polyelectrolyte complex coacervation method and characterized for their particle size, surface charge, morphology, mucoadhesive property, in-vitro and ex-vivo release, ocular tolerance, and antimicrobial efficacy studies. The pharmacodynamic study was conducted on rabbit eye model of induced keratitis and it is compared with marketed formulation (MF). Developed PENs showed the size range from 230.7 ± 0.64 to 249.0 ± 0.49 nm and positive surface charge, spherical shape along with appropriate physico-chemical parameters. Both in-vitro and ex-vivo examination concludes that PENs having more efficiency in sustained release of MXN compared to MF. Ocular irritation studies demonstrated that no corneal damage or ocular irritation. The in-vivo study proved that the anti-bacterial efficacy of PENs was improved when compared with MF. These results suggested that PENs are a feasible choice for MK therapy because of their ability to enhance ocular retention of loaded MXN through interaction with the corneal surface of the mucous membrane.

Design, synthesis and molecular modeling studies on novel moxifloxacin derivatives as potential antibacterial and antituberculosis agents.

Twenty-one novel alkyl/acyl/sulfonyl substituted fluoroquinolone derivatives were designed, synthesized and evaluated for their anti-tuberculosis and antibacterial activity. The targeted compounds were synthesized by the introduction of alkyl, acyl or sulfonyl moieties to the basic secondary amine moiety of moxifloxacin. Structures of the compounds were enlightened by FT-IR, 1H NMR, 13C NMR and HRMS data besides elemental analysis. Compounds were initially tested in vitro for their anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv using microplate alamar blue assay. Minimal inhibitory concentration (MIC) values of all compounds were found between > 25.00-0.39 µg/mL while compounds 1, 2 and 13 revealed an outstanding activity against M. tuberculosis H37Rv with MIC values of 0.39 µg/mL. Activities of compounds 1-21 against to a number of Gram-positive and Gram-negative bacteria and fast growing mycobacterium strain were also investigated by agar well diffusion and microdilution methods. According to antimicrobial activity results, compound 13 was found the most potent derivative with a IC50 value of <1.23 µg/mL against Staphylococcus aureus and clinical strain of methicillin-resistant clinical strain of S. aureus.