Physicochemical aspects of the coformulation of colistin and azithromycin using liposomes for combination antibiotic therapies.

Remote loading of azithromycin into liposomes, and subsequent release behavior in the presence of colistin, has been investigated with a view to understand the potential of liposomes to enable the coformulation of these two antibiotics for application in inhalation therapy. Azithromycin was successfully encapsulated into liposomes by remote loading (encapsulation efficiency > 98%). Slow release of azithromycin was achieved in the presence of cholesterol in a concentration-dependent manner, with a 4:1 mol ratio of phospholipid-cholesterol releasing 22% azithromycin in 24 h, whereas a 2:1 mol ratio released only 4.

Drug release from nanomedicines: Selection of appropriate encapsulation and release methodology.

The characterization of encapsulation efficiency and in vitro drug release from nanoparticle-based formulations often requires the separation of nanoparticles from unencapsulated drug. Inefficient separation of nanoparticles from the medium in which they are dispersed can lead to inaccurate estimates of encapsulation efficiency and drug release. This study establishes dynamic light scattering as a simple method for substantiation of the effectiveness of the separation process.

Interaction of colistin and colistin methanesulfonate with liposomes: colloidal aspects and implications for formulation.

Interaction of colistin and colistin methanesulfonate (CMS) with liposomes has been studied with the view to understanding the limitations to the use of liposomes as a more effective delivery system for pulmonary inhalation of this important class of antibiotic. Thus, in this study, liposomes containing colistin or CMS were prepared and characterized with respect to colloidal behavior and drug encapsulation and release. Association of anionic CMS with liposomes induced negative charge on the particles.

Self-assembly behavior of colistin and its prodrug colistin methanesulfonate: implications for solution stability and solubilization.

Colistin is an amphiphilic antibiotic that has re-emerged into clinical use due to the increasing prevalence of difficult-to-treat Gram-negative infections. The existence of self-assembling colloids in solutions of colistin and its derivative prodrug, colistin methanesulfonate (CMS), was investigated. Colistin and CMS reduced the air-water interfacial tension, and dynamic light scattering (DLS) studies showed the existence of 2.

Stability of colistin methanesulfonate in pharmaceutical products and solutions for administration to patients.

Colistin methanesulfonate (CMS) has the potential to hydrolyze in aqueous solution to liberate colistin, its microbiologically active and more toxic parent compound. While conversion of CMS to colistin in vivo is important for bactericidal activity, liberation of colistin during storage and/or use of pharmaceutical formulations may potentiate the toxicity of CMS. To date, there has been no information available regarding the stability of CMS in pharmaceutical preparations.

Subacute toxicity of colistin methanesulfonate in rats: comparison of various intravenous dosage regimens.

The relative nephro- and neurotoxicity of colistin methanesulfonate (CMS) was investigated with rats during 7 days of intravenous administration in regimens mimicking twice- and once-daily dosing of a clinically relevant dose for humans. Histological examination revealed more-severe renal lesions with the regimen corresponding to once-daily dosing, indicating that the potential for renal toxicity may be greater with extended-interval dosing.