title: Incorporation and controlled release of silyl ether prodrugs from PRINT nanoparticles.
abstract: 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.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Parrott
authors.forename: Mathew
authors.initials: M
authors.lastname: Finniss
authors.forename: J Chris
authors.initials: JC
authors.lastname: Luft
authors.forename: Ashish
authors.initials: A
authors.lastname: Pandya
authors.forename: Anuradha
authors.initials: A
authors.lastname: Gullapalli
authors.forename: Mary E
authors.initials: ME
authors.lastname: Napier
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DeSimone
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D000069439:Dasatinib; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004987:Ethers / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000008:administration & dosage* / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage* / Q000494:pharmacology; D012821:Silanes / Q000008:administration & dosage / Q000494:pharmacology; D013844:Thiazoles / Q000008:administration & dosage* / Q000494:pharmacology; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004987:Ethers; D011355:Prodrugs; D011743:Pyrimidines; D012821:Silanes; D013844:Thiazoles; D003841:Deoxycytidine; D000069439:Dasatinib; D002166:Camptothecin; D000093542:Gemcitabine