April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Resorbable Sustained Intra-Ocular Drug Release System for Monoclonal Antibodies & Other Large Molecules
Author Affiliations & Notes
  • S. M. Hampton
    TheraKine Ltd., Atlanta, Georgia
  • A. Voigt
    TheraKine Ltd., Atlanta, Georgia
  • A. Reiff
    Division of Rheumatology, Childrens Hospital Los Angeles, Los Angeles, California
  • Footnotes
    Commercial Relationships  S.M. Hampton, TheraKine, E; A. Voigt, TheraKine, E; A. Reiff, Abbott, Amgen, Merck, Pfizer, TheraKine, C.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5333. doi:
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      S. M. Hampton, A. Voigt, A. Reiff; Resorbable Sustained Intra-Ocular Drug Release System for Monoclonal Antibodies & Other Large Molecules. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5333.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Chronic inflammatory and diabetic eye diseases have been systemically treated with anti-tumor necrosis factor alpha therapies, which are limited by toxicity and cost. Therefore an intra-ocular sustained release system would be preferable, ideally intra-vitreal. Such a drug delivery system for biologic drugs would be resorbable and biocompatible in the eye, preserve the bioavailability and activity of the antibodies until they are released, and plausibly enable up to six months of release. Demonstration of key steps towards such a system are described.

Methods: : Multiple known biocompatible materials were tested for the encapsulation of an TNFa antibody. Once key candidates were selected, complexation concentrations with varying pH, ionic strength, and temperature were explored. The formulation(s) with the highest concentrations were then tested for bioavailability and their release profile.

Results: : The screening of different polymeric materials revealed that polyelectrolytes such as alginate and carboxymethylcellulose were best suited to form complexes with the antibody, reaching concentrations in excess of 200 mg/ml. Using an in-vitro assay for inhibition of NF kappa B activation in HeLa cells, bioavailability of this formulation (after cryopreservation and resuspension) was equivalent to an unformulated TNFa antibody. Drug release was characterized using an accelerated in-vitro model for two weeks, demonstrating an initial burst followed by linear release, compatible with a 2-month release period.

Conclusions: : We have demonstrated encapsulation of an TNFa monoclonal antibody with resorbable biopolymers. The system’s release profile is ideal for intra-ocular delivery of biologic drugs. In addition, we have been able to demonstrate preliminary success with a long term in-vitro sustained release system for up to 2 months. This method might be suitable for the delivery of other large molecules. Results of initial animal trials are presented separately.

Keywords: vitreous • inflammation • diabetic retinopathy 

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