Inhalable vancomycin-loaded lactose microparticles for treatment of MRSA pneumonia

The pulmonary route of administration is an attractive therapeutic approach to localize drug deposition for the treatment of lung infections. This route provides a passive targeting ability due to the direct delivery of the drug to the lungs, yet it requires a well-designed carrier to have suitable aerodynamic properties and avoid macrophage uptake. This study presents the design of an inhalable dry-powder formulation for localizing antibacterial activity against bacterial pneumonia. The proposed formulation is composed of vancomycin-conjugated iron oxide magnetic nanoparticles core and a lactose microparticle shell. The conjugation of vancomycin to the magnetic nanoparticles was conducted via the linkers (3-aminopropyl)trimethoxysilane and disuccinimidyl suberate while the microparticles were prepared using spray drying of the nanoparticles suspension in lactose. This formula was compared with our previously reported formulation composed of adsorbed vancomycin to magnetic nanoparticles core and spray-dried lactose/dextran shell. Physicochemical analysis of the prepared lactose microparticles showed a spherical morphology, thermal stability, and aerodynamic size of 2.2 ± 0.2 μm, which enables the vancomycin-conjugated nanoparticles to reach the infection site in the lung tissues. The formulation was then administered to healthy albino rats via a dry powder insufflator to assess the safety and pulmokinetics behaviorcompared to intravenous administration of the free drug. The results confirmed the successful accumulation of vancomycin in the lung tissues with enhanced safety profile on kidney and lung. Therefore, the developed nano-in-micro system showed potential for lung localization with the ability to treat MRSA pneumonia.