Incorporation and Controlled Release of Silyl Ether Prodrugs from PRINT Nanoparticles

Details

• Alternative Title:
  J Am Chem Soc
• Personal Author:
  Parrott, Matthew C. ; Finniss, Mathew ; Luft, J. Chris ; Pandya, Ashish ; Gullapalli, Anuradha ; Napier, Mary E. ; DeSimone, Joseph M.
• Description:
  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.
• Subjects:
  Antineoplastic Agents Apoptosis Camptothecin Cell Line, Tumor Dasatinib Delayed-Action Preparations Deoxycytidine Ethers Gemcitabine Humans Nanoparticles Neoplasms Prodrugs Pyrimidines Silanes Thiazoles

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• Source:
  J Am Chem Soc. 134(18):7978-7982
• Pubmed ID:
  22545784
• Pubmed Central ID:
  PMC3362319
• Document Type:
  Journal Article
• Funding:
  U54 CA119343/CA/NCI NIH HHSUnited States/ ; 1R01EB009565-02/EB/NIBIB NIH HHSUnited States/ ; R01 EB009565/EB/NIBIB NIH HHSUnited States/ ; U54CA119373/CA/NCI NIH HHSUnited States/ ; 1DP10D006432-01/DP/NCCDPHP CDC HHSUnited States/ ; U54 CA151652/CA/NCI NIH HHSUnited States/ ; DP1 CA174425/CA/NCI NIH HHSUnited States/ ; U54CA151652/CA/NCI NIH HHSUnited States/
• Volume:
  134
• Issue:
  18
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e29aad1327f6d20788c8777d296d9063b6281a05e4bf5512653b75d68f410ad4
• Download URL:
  https://stacks.cdc.gov/view/cdc/33375/cdc_33375_DS1.pdf
• File Type:
  [PDF - 1.59 MB ]