Ciprofloxacin-Loaded Nanocarriers with Passive and Active Targeting Potentials for Treating Infectious Pneumonia: Niosomes Conjugated with Isab Dna Ligands

The big challenge of the infectious pneumonia therapy is the invasion of drug-resistant bacteria such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). A possible resolution of this issue is the development of novel delivery systems containing conventional antibiotics. The application of nanomedicine on antibacterial therapy demonstrates some benefits, including the tiny and controllable particle size for formulation optimization, very high total surface area/volume ratio for close contact with bacteria, high affinity with bacteria after formulation modulation, and specific interaction to bacterial surface. Niosomes are nanovesicles containing nonionic surfactants and cholesterol for forming bilayer systems. They act as potential nanosystems for controlled drug delivery with nontoxicity, excellent stability, and ease of production. Moreover, niosomes are facile to scale-up in the industrial pharmacy. The main purpose of this proposal is to develop the ciprofloxacin-loaded niosomes with both passive and active targeting potentials for pulmonary delivery. The administration route is set as intravenous injection for killing MRSA and VRSA. The passive targeting ability of the niosomes is come from the incorporation of phosphatidylcholines or other phospholipids in the nanovesicles. These phospholipids are reported to be able to interact with pulmonary surfactants in the lung tissue. On the other hand, The active targeting ability of the niosomes is come from the conjugation of immunodominant surface antigen B (IsaB) DNA on noisome shell for showing affinity with IsaB protein on MRSA or VRSA membrane. The targeting strategy may result in a high ciprofloxacin concentration near the bacteria, leading to an efficient inhibition of these bacteria in lungs. The preliminary results showed a successful preparation of NLCs with sufficient stability, which demonstrated a diameter of about 120 nm. Ciprofloxacin exhibited a superior MRSA killing activity within THP-1 cells in the form of phosphatidylcholine-containing niosomes compared to control solution. The in vivo bioimaging revealed a high accumulation of phosphatidylcholine-containing niosomes in lungs than the control. The mechanisms about nanoparticle targeting to lungs are still unclear. We will also try to elucidate the mechanisms via cellular, in vitro, and in vivo experimental platforms. The purposes of each project in the three-year proposal are listed below:  The first year: Design and preparation of noisome formulations. Accomplishment of physicochemical characterization of the niosomes. The establishment of in vitro drug release profiles of ciprofloxacin.  The second year: Accomplishment of toxicity examination by cell level. Optimization of noisome formulations by the preliminary toxicity data. Evaluation of nanoparticle targeting by in vivo real-time bioimaging.  The third year: Establishment of animal models of infectious pneumonia. Performing pharmacokinetic and pharmacodynamic studies after ciprofloxacin-loaded noisome administration. Accomplishment of in vivo tolerance study by examining proteomics in various organs.

Project ID:PC10507-1230
External Project ID:MOST105-2320-B182-010-MY3