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ACS Nano. 2014 Jan 28;8(1):153-61. doi: 10.1021/nn4054107. Epub 2013 Dec 20.

Synthesis and evaluation of a nanoglobular dendrimer 5-aminosalicylic Acid conjugate with a hydrolyzable schiff base spacer for treating retinal degeneration.

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Department of Biomedical Engineering, School of Engineering, Case Western Reserve University , Cleveland, Ohio, United States.


Biocompatible dendrimers with well-defined nanosizes are increasingly being used as carriers for drug delivery. 5-Aminosalicylic acid (5-ASA) is an FDA-approved therapeutic agent recently found effective in treating retinal degeneration of animal models. Here, a water-soluble dendrimer conjugate of 5-ASA (AGFB-ASA) was designed to treat such retinal degeneration. The drug was conjugated to a generation 2 (G2) lysine dendrimer with a silsesquioxane core (nanoglobule) by using a hydrolyzable Schiff base spacer. Incubation of nanoglobular G2 dendrimer conjugates containing a 4-formylbenzoate (FB) Schiff base spacer in pH 7.4 phosphate buffers at 37 °C gradually released 5-ASA. Drug release from the dendrimer conjugate was significantly slower than from the low molecular weight free Schiff base of 5-ASA (FB-ASA). 5-ASA release from the dendrimer conjugate was dependent on steric hindrance around the spacer. After intraperitoneal injection, the nanoglobular 5-ASA conjugate provided more effective 7-day protection against light-induced retinal degeneration at a reduced dose than free 5-ASA in Abca4(-/-)Rdh8(-/-) mice. The dendrimer 5-ASA conjugate with a degradable spacer could be a good candidate for controlled delivery of 5-ASA to the eye for treatment of retinal degeneration.

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