In Vitro, In Vivo, and In Silico Evaluation of the Bioresponsive Behavior of an Intelligent Intraocular Implant
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.
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.
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.
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.
KEY WORDSin vivo test inflammation intraocular implant molecular modeling physicochemical properties physicomechanical properties stimulus-responsive
Bioresponsive polymeric matrices
Intelligent Intraocular Implant
- Lipo-CHT-PCL NS
Molecular Mechanics Energy Relationships
Stimulus-responsive hydrogel system
Simulated vitreous humor
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