Preparation of hybrid silver/ciprofloxacin nanoparticles for pulmonary drug delivery

Hisham Al-Obaidi, Mridul Majumder

Background. Ciprofloxacin (CFX) is a fluroquinolone antibiotic used as a first line treatment against infections caused by pseudomonas aeruginosa and streptococcus pneumonia, which are commonly, acquired by cystic fibrosis (CF) patients. However, no inhalation formulation is currently available for ciprofloxacin. A major problem with orally administered CP is the poor penetration through the thick mucus typically exists in CF. Silver has been shown to exert mucolytic activity hence a combination with CFX would be a potential approach to improve drug deposition. The aim of this study is to develop novel hybrid nanoparticles of CFX and silver coated with layers of silica. Coating with silica is essential to ensure uniform distribution of silver nanoaprticles as well as to prevent possible aggregation. The final particles are able to exert mucolytic activity as well as enhanced antibacterial activity. The matrix is formed of chitosan, which is a cationic polysaccharide able to further improve mucus adhesion.
Methods. Silica coated silver nanoparticles were prepared using Stöber method based on hydrolysis of tetraethyl orthosilicate (TEOS) and analysed by photo correlation spectroscopy and transmission electron microscopy. The optimum ratio of chitosan and sodium triphosphate was used to encapsulate CFX. Particle deposition was assessed in vitro using twin stage impinge using Rotahaler device and based on peak flow of 50L/min.
Results. Successful coating with silica was achieved using dimethylamine as a catalyst. Size measurements showed that the size of the silica coated silver nanoparticles ranged between 100-200nm. Entrapment efficiency % showed consistent results with approximate value of approximately 40% CFX. In vitro deposition results showed significant deposition in stage 2 using twin stage impinger (TSI) (~70%).
Conclusions. Hybrid nanoparticles of silica coated-silver embedded in chitosan matrix and encapsulating ciprofloxacin were successfully prepared. The particles were significantly deposited into the second stage of TSI with some oropharyngeal deposition.

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