ABSTRACT
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.
Subject(s)
Ciprofloxacin/administration & dosage , Escherichia coli/drug effects , Glucans/chemistry , Nanocapsules/administration & dosage , Nanocapsules/chemistry , Polyesters/chemistry , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Cell Survival/drug effects , Cell Survival/physiology , Ciprofloxacin/chemistry , Diffusion , Escherichia coli/physiology , Materials Testing , Nanocapsules/ultrastructure , Nanospheres/administration & dosage , Nanospheres/chemistry , Nanospheres/ultrastructure , PorosityABSTRACT
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.
Subject(s)
Anti-Infective Agents/administration & dosage , Ciprofloxacin/administration & dosage , Contact Lenses, Hydrophilic , Drug Delivery Systems , Nanospheres , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Colony Count, Microbial , Delayed-Action Preparations , Glucans/chemistry , Humans , Microbial Sensitivity Tests , Microscopy, Atomic Force , Polyesters/chemistry , Pseudomonas aeruginosa/physiology , Staphylococcus aureus/physiologyABSTRACT
The material properties of silk are favorable for drug delivery due to the ability to control material structure and morphology under ambient, aqueous processing conditions. Mass transport of compounds with varying physical-chemical characteristics was studied in silk fibroin films with control of ß-sheet crystalline content. Two compounds, vitamin B12 and fluorescein isothiocynate (FITC) labeled lysozyme were studied in a diffusion apparatus to determine transport through silk films. The films exhibited size exclusion phenomenon with permeability coefficients with contrasting trends with increases in ß-sheet crystallinity. The size exclusion phenomenon observed with the two model compounds was characterized by contrasting trends in permeability coefficients of the films as a function of ß-sheet crystallinity. The diffusivity of the compounds was examined in the context of free volume theory. Apart from the ß-sheet crystallinity, size of the compound and its interactions with silk influenced mass transfer. Diffusivity of vitamin B12 was modeled to define a power law relationship with ß-sheet crystallinity. The results of the study demonstrate that diffusion of therapeutic agents though silk fibroin films can be directed to match a desired rate by modulating secondary structure of the silk proteins.
ABSTRACT
The functional properties of six distinct electrospun silk material groups were evaluated to assess conformational and biocompatible characteristics related to wound dressings. In a hydrated state, all six silk matrices exhibited absorption, water vapor transmission, oxygen permeation and enzymatic biodegradation suitable for full-thickness wound sites. Employing constrained drying techniques, silk concentration was a determinate factor influencing material structural properties related to the storage and distribution of such wound dressing systems. Subsequently, three electrospun silk models demonstrated ideal biomaterial properties with potential utility for wound dressings.
