The Influence of Lipid Matrix Composition on the Microenvironment of Levofloxacin in Liposomal Forms

Abstract

— We have studied the interaction of the antibacterial drug levofloxacin with lipid bilayers of various compositions: 100% DPPC and with the addition of 20% cardiolipin. For DPPC liposomes, levofloxacin was found to penetrate into the subpolar region at the lipid–water interface. The role of the anionic lipid in the interaction of an active molecule with a bilayer has been established: levofloxacin enters the microenvironment of the phosphate group, displacing water, and does not penetrate into the hydrophobic part of the bilayer. For the first time, the study of the microenvironment of levofloxacin in the liposome by IR and CD spectroscopy was carried out. Such an approach based on a combination of several spectral methods opens up new prospects for the creation of new medicinal properties and the possibility of predicting the nature of the interaction of active molecules with biomembranes in order to predict their efficacy and potential side effects.

Liposomal Forms of Fluoroquinolones and Antifibrotics Decorated with Mannosylated Chitosan for Inhalation Drug Delivery

“…Tightening of the DPPC membrane by introducing 10% cholesterol did not lead to a significant change in the efficiency of loading levofloxacin. This correlates well with previous data that levofloxacin does not tend to interact extensively with the lipid-water interface [16,45].…”

“…We have previously conducted primary studies on the physicochemical properties of liposomal moxifloxacin (DPPC:CL 80:20) [14], levofloxacin (DPPC and DPPC:CL 80:20) [16,45], and pirfenidone (DPPC and DPPC:Chol 90:10) [46]. Here, we aim to conduct a fundamental analysis of the influence of the composition of the lipid matrix on the properties of the liposomal form of these drugs.…”

“…To solve this problem, we propose to use the approach developed in our laboratory consisting of loading the drug into liquid-polymer nanoparticles [12,13]. Previously, we studied the effect of polymer properties on the structural and functional properties of liposomal forms of fluoroquinolones (moxifloxacin [14,15] and levofloxacin [16]) using PEGylated and mannosylated chitosan derivatives. We found the way to fine tailor liquidpolymer nanoparticles by means of variations of chitosan derivative nature, e.g., varying storage stability, controlled release, etc.…”

Conjugates of Chitosan with β-Cyclodextrins as Promising Carriers for the Delivery of Levofloxacin: Spectral and Microbiological Studies

“…As an alternative delivery system for inhaled levofloxacin, liposomal systems are considered, for example, in [ 47 , 48 , 49 ]. On the one hand, liposomes have a high biocapacity and allow a prolonged release of the contents; for example, in [ 47 ], the release of half of the loaded drug is observed after only 15 h. On the other hand, the production of liposomes and the control of their physico-chemical properties is a much more difficult task compared to the production of chitosan conjugates with cyclodextrin.…”

“…On the one hand, liposomes have a high biocapacity and allow a prolonged release of the contents; for example, in [ 47 ], the release of half of the loaded drug is observed after only 15 h. On the other hand, the production of liposomes and the control of their physico-chemical properties is a much more difficult task compared to the production of chitosan conjugates with cyclodextrin. Moreover, the drug: carrier mass ratios for liposomes loaded with levofloxacin range from 2 to 7% [ 47 , 49 ], while for complexes with conjugates herein, the calculated ratio reaches 20%. Thus, chitosan conjugates with cyclodextrin represent an undoubted interest for further research as a delivery system for antibacterial drugs.…”