Synthesis and characterization of pullulan-polycaprolactone core-shell nanospheres encapsulated with ciprofloxacin.

Nanosphere-encapsulated drugs offer a means to overcome many drug delivery limitations by localizing the site of delivery and providing controlled release. This research details the synthesis and encapsulation of ciprofloxacin in pullulan-polycaprolactone (PCL) core shell nanospheres and the characterization of these materials by 1H-NMR, UV spectroscopy, dynamic light scattering (DLS) and scanning electron microscopy (SEM).1H-NMR results confirm that the pullulan-PCL grafted copolymer was successfully synthesized. UV spectroscopy showed that the ciprofloxacin loaded nanospheres contain 35-40% ciprofloxacin by weight. DLS and SEM results indicate that the loaded nanospheres are spherical in shape and approximately 142+/-12 nm in size. Under in vitro test conditions, approximately 20% of the ciprofloxacin is released in the first 4 hours, with additional release over 10 days. The nanoparticles demonstrate bioactivity against Escheria coli and do not affect the proliferation of two human cell lines. These results demonstrate the potential of pullulan-PCL core-shell nanospheres as delivery vehicles of hydrophobic drugs, including antibiotics for localized treatments applicable to a wide-range of human bacterial infections.

Sustained ocular delivery of ciprofloxacin using nanospheres and conventional contact lens materials.

PURPOSE: To formulate conventional contact lenses that incorporate nanosphere-encapsulated antibiotic and demonstrate that the lenses provide for sustained antibacterial activity. METHODS: A copolymer composed of pullulan and polycaprolactone (PCL) was used to synthesize core-shell nanospheres that encapsulated ciprofloxacin. Bactericidal activity of the nanosphere-encapsulated ciprofloxacin (nanosphere/cipro) was tested by using liquid cultures of either Staphylococcus aureus or Pseudomonas aeruginosa. Nanosphere/cipro was then incorporated into HEMA-based contact lenses that were tested for growth inhibition of S. aureus or P. aeruginosa in liquid cultures inoculated daily with fresh bacteria. Lens designs included thin or thick lenses incorporating nanosphere/cipro and ciprofloxacin-HCl-soaked Acuvue lenses (Acuvue; Johnson & Johnson Vision Care, Inc., Jacksonville, FL). RESULTS: Less than 2 µg/mL of nanosphere/cipro effectively inhibited the proliferation of cultures inoculated with 10(7) or 10(8) bacteria/mL of S. aureus and P. aeruginosa, respectively. HEMA-based contact lenses polymerized with nanosphere/cipro were transparent, effectively inhibited the proliferation of greater than 10(7)/mL of bacteria added daily over 3 days of culture, and killed up to 5 × 10(9) total microbes in a single inoculation. A thicker lens design provided additional inhibition of bacterial growth for up to 96 hours. CONCLUSIONS: Core-shell nanospheres loaded with an antibiotic can be incorporated into a conventional, transparent contact lens and provide for sustained and effective bactericidal activity and thereby provide a new drug delivery platform for widespread use in treating ocular disorders.