Design and Synthesis of Long-Acting Doxorubicin Derivatives Aiming Targeted Delivery and Enhanced Drug Translocation
| Autor: | Chuan-Hui Lu, 盧泉潓 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 In this study, we designed and synthesized the novel doxorubicin (DOX) formulation for enhanced drug delivery and cancer cell targeting. A cell-penetrating peptide (CPP), Indolicidin analogue, was covalently conjugated to DOX and acted as a transmembrane carrier for enhancing drug translocation into HepG2 cells. The DOX-CPP conjugates enhanced the translocation of DOX into HepG2 cell, resulting in higher anticancer activity. Furthermore, the bioinert polymer, polyethylene glycol (PEG), was conjugated to CPP for prolonging in vivo drug circulation. Matrix metalloproteinase-2 (MMP-2) cleavable sequences were designed, and added at the N-terminal of CPP. The PEG segment could be detached from DOX-CPP in the presence of MMP-2. It was found that the half-life in trypsin after PEG-5K protection could be increased from 10 minutes to 4 hours. And the enhanced penetration could be observed after MMP-2 cleavage. Thus, this DOX formulation is able to be a potential to apply in pharmaceutical use. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|