Incorporation and Controlled Release of Silyl Ether Prodrugs from PRINT Nanoparticles

Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Journal of the American Chemical Society (Impact Factor: 12.11). 04/2012; 134(18):7978-82. DOI: 10.1021/ja301710z
Source: PubMed


Asymmetric bifunctional silyl ether (ABS) prodrugs of chemotherapeutics were synthesized and incorporated within 200 nm × 200 nm particles. ABS prodrugs of gemcitabine were selected as model compounds because of the difficulty to encapsulate a water-soluble drug within a hydrogel. The resulting drug delivery systems were degraded under acidic conditions and were found to release only the parent or active drug. Furthermore, changing the steric bulk of the alkyl substituents on the silicon atom could regulate the rate of drug release and, therefore, the intracellular toxicity of the gemcitabine-loaded particles. This yielded a family of novel nanoparticles that could be tuned to release drug over the course of hours, days, or months.

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Available from: James Christopher Luft, May 07, 2015
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    • "These studies will test the hypothesis that targeted modulation of lung immunology via nanoengineering may enable a new class of therapeutics for lung disorders that avoid systemic side-effects while also reducing administration doses. While we have tested a 50 µg dose of inert particles in this manuscript, PRINT enables a high weight percent loading of bioactive molecules and thus local and sustained pulmonary delivery may show therapeutic efficacy at low particle doses [19]–[22], [66]–[68]. "
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