Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina

Gauri P. Misra, Ravi S.J. Singh, Tomas S. Aleman, Samuel G. Jacobson, Thomas W. Gardner, Tao Lowe

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The objective of this work is to develop subconjunctivally implantable, biodegradable hydrogels for sustained release of intact insulin to the retina to prevent and treat retinal neurovascular degeneration such as diabetic retinopathy. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-(2-hydroxyetheyl methacrylate) units (Dex-lactateHEMA) in 25:75 (v:v) ethanol:water mixture solvent. Insulin is loaded into the hydrogels during the synthesis process with loading efficiency up to 98%. The hydrogels can release biologically active insulin in vitro for at least one week and the release kinetics can be modulated by varying the ratio between NIPAAm and Dex-lactateHEMA and altering the physical size of the hydrogels. The hydrogels are not toxic to R28 retinal neuron cells in culture medium with 100% cell viability. The hydrogels can be implanted under the conjunctiva without causing adverse effects to the retina based on hematoxylin and eosin stain, immunostaining for microglial cell activation, and electroretinography. These subconjunctivally implantable hydrogels have potential for long-term periocular delivery of insulin or other drugs to treat diabetic retinopathy and other retinal diseases.

Original languageEnglish (US)
Pages (from-to)6541-6547
Number of pages7
JournalBiomaterials
Volume30
Issue number33
DOIs
StatePublished - Nov 1 2009

Fingerprint

Hydrogels
Insulin
Retina
Diabetic Retinopathy
Retinal Neurons
Electroretinography
Retinal Diseases
Retinal Degeneration
Dextran
Methacrylates
Photopolymerization
Poisons
Conjunctiva
Hematoxylin
Eosine Yellowish-(YS)
Dextrans
Cell culture
Neurons
Culture Media
Cell Survival

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina. / Misra, Gauri P.; Singh, Ravi S.J.; Aleman, Tomas S.; Jacobson, Samuel G.; Gardner, Thomas W.; Lowe, Tao.

In: Biomaterials, Vol. 30, No. 33, 01.11.2009, p. 6541-6547.

Research output: Contribution to journalArticle

Misra, Gauri P. ; Singh, Ravi S.J. ; Aleman, Tomas S. ; Jacobson, Samuel G. ; Gardner, Thomas W. ; Lowe, Tao. / Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina. In: Biomaterials. 2009 ; Vol. 30, No. 33. pp. 6541-6547.
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