Purchase this article with an account.
M. Burkstrand, N. R. F. Beeley, S. E. Varner, S. Chudzik; Biodegradable Polysaccharide Devices for the Controlled Delivery of Bioactive Agents. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5802.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Evaluate feasibility of an enzymatically-controlled degradable polysaccharide matrix system for sustained, controlled release of bioactive proteins in the vitreous.
Rod-shaped devices 5 mm in length and 0.5 mm in diameter were formed using modified, low molecular weight polysaccharides (PS) and incorporating known amounts of a 49 kD rabbit-anti-goat antibody fragment [f(ab)] as a model protein. Devices containing f(ab) [PS Formulation 1, with 53 ug of f(ab); PS Formulation 2 with 73 ug f(ab)] were implanted in the vitreous of Dutch-belted rabbit eyes. At 7, 28, and 56 days, the devices were explanted and assayed for remaining active and total f(ab) using ELISA. Vitreous samples at these timepoints were similarly assayed via ELISA for active f(ab).
Of the 29 implanted animals, all remained in good general health throughout the study. Follow-up clinical examinations reflected good biocompatibility tolerance. Following enucleation, the devices were removed from the eyes either fully intact, or in smaller, multiple pieces. Explantated Formulation 1 devices showed an average f(ab) activity (active f(ab)/total f(ab)) of 76, 71, and 86% at day 7, 28, and 56 timepoints, respectively, while Formulation 2 devices showed f(ab) activity of 76% at days 7 and 28. No f(ab) was detected in the explanted devices at day 56 for Formulation 2. Mass-loss calculations on day 56 explants showed Formulation 1 lost approximately 63% of the device mass, while Formulation 2 lost approximately 80% of the device mass. Average active f(ab) detected in the vitreous for the Formulation 1 group was 1.6, 1.3 and 0.1 ug/g, and 2.2, 0.95, and 0.2 ug/g for the Formulation 2 group at days 7, 28, and 56 respectively.
It is possible to form devices from modified, low molecular weight polysaccharides that have sufficient density to inhibit the diffusion of entrained proteins through the matrix and exclude digesting enzymes from penetrating the matrix. The polysaccharide devices were demonstrated to be safe and well tolerated in this study. The implanted devices showed sustained delivery of substantial active f(ab) molecule into the vitreous at each timepoint, while the remaining f(ab) in the explanted devices remained stable at each timepoint, as demonstrated by the high % retained activity.
This PDF is available to Subscribers Only