Du Toit L.C., Carmichael T., Govender T., Kumar P., Choonara Y.E., Pillay V.
Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, 2193 Johannesburg, South Africa; Department of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, 2193 Johannesburg, South Africa; Department of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu, Natal University Road Westville, 4000 Durban, South Africa
Du Toit, L.C., Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, 2193 Johannesburg, South Africa; Carmichael, T., Department of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, 2193 Johannesburg, South Africa; Govender, T., Department of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu, Natal University Road Westville, 4000 Durban, South Africa; Kumar, P., Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, 2193 Johannesburg, South Africa; Choonara, Y.E., Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, 2193 Johannesburg, South Africa; Pillay, V., Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, 2193 Johannesburg, South Africa
Purpose: An autofeedback complex polymeric platform was used in the design of an intelligent intraocular implant - the I3 - using stimuli-responsive polymers, producing a smart release system capable of delivering therapeutic levels of an anti-inflammatory agent (indomethacin) and antibiotic (ciprofloxacin) for posterior segment disorders of the eye in response to inflammation. Methods: Physicochemical and physicomechanical analysis of the I3 was undertaken to explicate the highly crosslinked make-up and 'on-off' inflammation-responsive performance of the I3. In addition, energetic profiles for important complexation reactions were generated using Molecular Mechanics Energy Relationships by exploring the spatial disposition of energy minimized molecular structures. Furthermore, preliminary in vivo determination of the inflammation-responsiveness of the I3 was ascertained following implantation in the normal and inflamed rabbit eye. Results: In silico modeling simulating a pathological inflammatory intraocular state highlighted the interaction potential of hydroxyl radicals with the selected polysaccharides comprising the I3. The intricately crosslinked polymeric system forming the I3 thus responded at an innate level predicted by its molecular make-up to inflammatory conditions as indicated by the results of the drug release studies, rheological analysis, magnetic resonance imaging and scanning electron microscopic imaging. In vivo drug release analysis demonstrated indomethacin levels of 0.749 ± 0.126 μg/mL and 1.168 ± 0.186 μg/mL, and ciprofloxacin levels of 1.181 ± 0.150 μg/mL and 6.653 ± 0.605 μg/mL in the normal and inflamed eye, respectively. Conclusions: Extensive in vitro, molecular, and in vivo characterization therefore highlighted successful inflammation- responsiveness of the I3. The I3 is a proposed step forward from other described ocular systems owing to its combined bioresponsive, nano-enabled architecture. © 2013 Springer Science+Business Media New York.
ciprofloxacin; hydroxyl radical; indometacin; polymer; polysaccharide; animal experiment; animal model; article; blood rheology; chemical structure; computer model; controlled study; cross linking; differential scanning calorimetry; drug release; energy; eye inflammation; in vitro study; in vivo study; infrared spectroscopy; intelligent intraocular implant; lens implant; molecular mechanics; molecular model; nonhuman; nuclear magnetic resonance imaging; oscillation; physical chemistry; posterior eye segment; priority journal; rabbit; scanning electron microscopy; thermal analysis; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ciprofloxacin; Computer Simulation; Drug Delivery Systems; Eye; Eye, Artificial; Indomethacin; Inflammation; Polymers; Polysaccharides; Rabbits