Rifampicin Loaded Mannosylated Cationic Nanostructured Lipid Carriers for Alveolar Macrophage-specific Delivery

• DOI: 10.1007/s11095-014-1572-3
• Publication Date: 2014-11-21T10:57:00Z
• Authors: Xu Song; Qing Lin; Ling Guo; Yao Fu; Jianfeng Han; Huan Ke; Xun Sun; Tao Gong; Zhirong Zhang
• Keywords: Male; Drug Carriers; 0303 health sciences; Lipids; Cell Line; Nanostructures; Mice; 03 medical and health sciences; Drug Delivery Systems; Macrophages, Alveolar; Animals; Humans; Tissue Distribution; Particle Size; Rats, Wistar; Rifampin; Antibiotics, Antitubercular; Mannose

In this study, cationic mannosylated nanostructured lipid carriers (Man-NLCs) were developed for the targeted delivery of rifampicin to alveolar macrophages.Rifampicin loaded Man-NLCs (RFP-Man-NLCs) and rifampicin loaded unmodified nanostructured lipid carriers (REP-NLCs) were prepared using thin film homogenization method and characterized by particle size, polydispersity index, zeta potential, transmission electron microscopy, encapsulation efficiency, pharmacokinetics, biodistribution, cell specific targeting, cytotoxicity and inflammatory response.RFP-Man-NLCs and REP-NLCs obtained displayed a size distribution around 160 nm (PDI <0.30) with positive charges of approximately 30 mV. The encapsulation efficiency of RFP was above 90%. In the biodistribution study, both RFP-Man-NLCs and RFP-NLCs, compared with the commercially available rifampicin solution, displayed superior lung-targeting ability. Compared to REP-NLCs, RFP-Man-NLCs exhibited significantly higher uptake efficiency in NR8383 cells and alveolar macrophages, which achieved cell-specific targeting. In addition, RFP-Man-NLCs were demonstrated to be a safe formulation with minimum toxicity and no inflammatory response.RFP-Man-NLCs provided an alternative strategy for selectively delivering rifampicin to alveolar macrophages.