Development of liposomal formulations of Moxifloxacin for intraocular administration for the therapy/prevention of post-operative endopthalmitis

• Κύριος συγγραφέας: Νατσαρίδης, Ευάγγελος
• Άλλοι συγγραφείς: Natsaridis, Evangelos
• Γλώσσα: English
• Έκδοση: 2022
• Θέματα: Liposomes; Moxifloxacin; DRV; Active loading; Microfluidics; Antibacterial; Λιποσώματα; Μοξιφλοξασίνη; Ενεργή φόρτωση; Ανάμειξ΄η υπό μικρορροή; Αντιβακτηριακή δράση

Postoperative endophthalmitis is a common severe intraocular infection, which, when remaining incurable, can lead to permanent loss of vision. The past few years, several antibiotics have been utilized for treatment or prophylaxis of/from post-cataract-surgery endophthalmitis, and one of them is the fourth-generation fluoroquinolone antibiotic moxifloxacin (MOX). MOX is mainly administered as a solution topically, on the eye surface in the form of drops, however, because of its limited residence time in the area and low permeability through the several ocular barriers of the eye, and consequently the low bioavailability in the posterior part of the eye, its action is limited, leading to short protection and the need for daily dose repetitions. The development of innovative intravitreal injection forms that release MOX in a controlled manner will have a major impact on the treatment as well as the prevention of severe postoperative infections. Among the advanced carriers of drugs, liposomes are the most biocompatible and non-toxic that offer increased drug incorporation, prolongation of drug action time (controlled release rate), ability to target specific cells, protection of active ingredients, ability to overcome biological barriers, etc. In the present thesis, we aimed to develop optimal sustained release MOX loaded liposomes, as intraocular therapeutic agents for endophthalmitis. Three methods were used for the preparation of MOX loaded liposomes, the passive loading Dehydration-Rehydration (DRV) method and two active loading liposome preparation methods; the “conventional” Active or Remote Loading method (AL) and a newly developed herein method comprising alternative Microfluidic mixing cycles (MF). Numerous lipid-membrane compositions were used to determine potential effect on MOX loading and retention in liposomes, while the different preparation methods were also compared in regards to their antibacterial effects against S. Epidermidis and S. aureus bacterial strains, in planctonic bacteria as well as in biofilms. The active loading methods conferred liposomes with higher MOX encapsulation compared to the DRV method, for all the lipid compositions used, while they also demonstrated substantially higher antimicrobial potential towards S. epidermidis growth and biofilm susceptibility, compared to corresponding DRV liposomes, indicating the importance of sustained MOX retention into liposomes, on their activity. Additionally, Cholesterol (Chol) incorporation into the liposome membrane is demonstrated to be a key factor, influencing the antimicrobial efficacy of liposomal MOX towards S. epidermidis and S. aureus bacterial strains. Furthermore, interestingly, the lipid amount that carries a given amount of MOX was also found to have a significant effect on MOX-liposome antimicrobial activity, suggesting that as the number of MOX-loaded vesicles that come into contact with bacteria increases, so does the overall antimicrobial effect. Concluding, the liposome preparation method/type, the lipid concentration that is incubated with the bacteria (and thereby the number of vesicles/nanoparticles that interacts with a given number of bacterial cells), and also the Chol molar ratio of liposomal MOX, determine the antibacterial properties of MOX-loaded liposomes towards planktonic bacteria and also towards biofilm-forming ones, possibly due to the different percent of MOX retention in the liposomes under the different conditions applying. The current findings are particularly interesting and deserve further in vitro and in vivo investigations.