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C. D. Leahy, E. E. Ellis, S. P. McCarthy, P. Gaines, S. Shady, K. S. Crawford; Sustained Antibiotic Delivery From Nanospheres Within Contact Lens Hydrogels. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3419.
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© ARVO (1962-2015); The Authors (2016-present)
Improved delivery of ophthalmic drugs such as antibiotics is critical for increased patient compliance, efficacy and convenience. Initial pulse dosing followed by sustained release of antibiotics from a contact lens delivery system offers significant advantages over a regimen of frequent, tapering administration of eyedrops. Ciprofloxacin (Cipro) was encapsulated into biodegradable nanospheres and incorporated into a 38% poly HEMA hydrogel matrix. Synthesis was customized to achieve release of antimicrobial concentrations of Cipro over an extended period of time.
Nanosphere Synthesis: Amphiphilic copolymers were formed by coupling pullulan with PCL. Copolymer self-assembled into shell-core nanospheres upon dilution with water, which encapsulated Cipro and were lyophilized after purification by dialysis. Nanospheres were characterized by Atomic Force Microscopy, NMR, SEM, and TGA analyses, which identified particle size of 130-160nm, containing 35-40% Cipro by weight. Nanospheres dispersed in water were added to HEMA, and polymerized by exposure to UV. Release profile of Cipro from both nanospheres and hydrogel-nanosphere matrix was determined spectrophotometrically. Antimicrobial activityies of nanospheres containing Cipro and hydrogel-nanosphere- matrix were assessed by examining changes in growth curves by turbidity measurements of bacterial cultures.
Modifications at various steps in the synthesis procedures impacted on nanosphere solubility and clarity, Cipro concentration, and release profile. The Cipro-loaded nanospheres proved to have comparable antimicrobial activity to free Cipro, with MIC values in the range of 1-10 µg/mL. Cipro-encapsulated nanospheres were developed that readily dispersed into a solution that was incorporated into a hydrogel matrix at concentrations up to 1:50 nanosphere:hydrogel ratio. Prototype devices demonstrated an initial pulse dose of 133 µg over 24 hr, followed by slow, sustained release of 1-10 µg Cipro/day over a 14 day period.
This initial pulse dose followed by slow release of Cipro for up to 14 days could provide the appropriate sustained delivery and improved compliance to replace initially frequent and tapering dose drop therapy for ocular surface infections. This technology also shows promise for bandage contact lenses for pre- and post-surgical prophylactic delivery of antibiotics over a 1-2 week period.
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