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S.K. Ray, K.G. Carrasquillo, I. Rigas, P. Calias, J.W. Miller, E.S. Gragoudas, A.P. Adamis; Encapsulation of Anti-ICAM-1 Antibodies into PLA-PEG Microspheres: In vitro and in vivo Characterization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4450.
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Purpose: To develop a sustained delivery system for the inhibition of intercellular adhesion molecule (ICAM-1). Methods: Anti-human ICAM1 antibody solid-state formulations, containing trehalose and histidine as excipients, were encapsulated into PLA-PEG (70/30) polymer microspheres. In vitro experiments were performed to characterize the release profiles and determine the bioactivity and stability of the released antibodies. Bioactivity was assessed by monitoring the ability of the antibody to inhibit ICAM-1-mediated leukocyte adhesion to human umbilical vein endothelial cells. To investigate the feasibility of transcleral delivery, a PDMS device was packed with microspheres and placed on the sclera of Dutch belted rabbits. At selected time points, ocular tissues were isolated and the amount of delivered antibody was determined by ELISA. Results: PLA-PEG microspheres were able to deliver ICAM-1 antibodies in a sustained manner, at an average rate of 30 µg/day over a 20-day period. The leukocyte-adhesion assay verified that the antibodies retained their bioactivity, demonstrating compatibility with the encapsulation process. Ocular tissue analysis revealed significant antibody levels, supporting the utility of transcleral delivery for this antibody. Conclusions: The feasibility of encapsulating ICAM-1 antibodies into polymer microspheres and delivering then in a bioactive state over a period of 20 days was demonstrated. In vivo experiments in rabbits indicate that transcleral delivery is a feasible method for the delivery of encapsulated antibodies.
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