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Pharmaceutical Research

, Volume 31, Issue 3, pp 607–634 | Cite as

In Vitro, In Vivo, and In Silico Evaluation of the Bioresponsive Behavior of an Intelligent Intraocular Implant

  • Lisa C. du Toit
  • Trevor Carmichael
  • Thirumala Govender
  • Pradeep Kumar
  • Yahya E. Choonara
  • Viness PillayEmail author
Research Paper

ABSTRACT

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.

KEY WORDS

in vivo test inflammation intraocular implant molecular modeling physicochemical properties physicomechanical properties stimulus-responsive 

ABBREVIATIONS

ALG

Alginate

BPMs

Bioresponsive polymeric matrices

CMV

Cytomegalovirus

DCC

N,N′-dicyclohexylcarbodiimide

DSPC

Distearoylphosphatidylcholine

DSPE

Distearoylphosphatidylethanolamine

HA

Hyaluronic acid

I3

Intelligent Intraocular Implant

Lipo-CHT-PCL NS

Lipoidal-chitosan-poly(ε-caprolactone) nanosystem

LPS

Lipopolysaccharide

MMER

Molecular Mechanics Energy Relationships

NS

Nanosystem/s

OH

Hydroxyl radicals

PAA

Poly(acrylic acid)

PCL

Poly(ε-caprolactone)

SRHS

Stimulus-responsive hydrogel system

SVH

Simulated vitreous humor

Supplementary material

ESM 1

(WMV 4278 kb)

11095_2013_1184_MOESM2_ESM.docx (20 kb)
Supplementary Table I (DOCX 19 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Lisa C. du Toit
    • 1
  • Trevor Carmichael
    • 2
  • Thirumala Govender
    • 3
  • Pradeep Kumar
    • 1
  • Yahya E. Choonara
    • 1
  • Viness Pillay
    • 1
    Email author
  1. 1.Department of Pharmacy and Pharmacology, Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
  2. 2.Ophthalmology Division, Department of Neurosciences Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
  3. 3.Department of Pharmaceutical Sciences, School of Health SciencesUniversity of KwaZulu NatalDurbanSouth Africa

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