Triggered release of ciprofloxacin from nanostructured agglomerated vesicles

Nanostructured agglomerated vesicles encapsulating ciprofloxacin were evaluated for modulated delivery from the lungs in a healthy rabbit model. An aliphatic disulfide crosslinker, cleavable by cysteine was used to form cross-links between nanosized liposomes to form the agglomerates. The blood levels of drug after pulmonary instillation of free ciprofloxacin, liposomal ciprofloxacin, and the agglomerated liposomes encapsulating ciprofloxacin were evaluated. The liposomes and agglomerated vesicles showed extended release of drug into the blood over 24 hours, while the free ciprofloxacin did not. The agglomerates also allowed modulation of the drug release rate upon the introduction of cysteine into the lungs post-drug instillation; the cysteine-cleavable agglomerates accelerated their drug release rate, indicated by an increased level of drug in the blood. This technology holds promise for the post-administration modulation of antibiotic release, for the prevention and treatment of pulmonary and systemic infections.