Abstract
Aim: Proteasome inhibitors, such as carfilzomib (CFZ), have shown potential to treat various types of cancers in preclinical models, but clinical applications are limited likely due to formulation and delivery issues. Results & methodology: Tethered polymer nanoassemblies (TNAs) were synthesized by tethering hydrophilic polymers and hydrophobic groups to charged polymer scaffolds, and then end-capping remaining amines on scaffold. Drug entrapment and drug release half-lives increased as charge was removed from scaffold. TNAs with sustained CFZ release maintained drug efficacy after preincubation and increased duration of proteasome inhibition in cancer cells compared with free CFZ. Conclusion: TNAs fine-tuned CFZ release as charge was removed from polymer scaffold, which allowed for sustained proteasome inhibition in cancer cells and potentially enhanced anticancer efficacy.
| Original language | English |
|---|---|
| Pages (from-to) | 665-681 |
| Number of pages | 17 |
| Journal | Therapeutic Delivery |
| Volume | 7 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2016 |
Bibliographical note
Publisher Copyright:© 2016 Future Science Ltd.
Funding
Wooin Lee acknowledges financial support from Basic Science Research Program, National Research Foundation of Korea, Ministry of Science, ICT and Future Planning (NRF-2014R1A1A3050645). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
| Funders | Funder number |
|---|---|
| Basic Science Research Program | |
| Ministry of Science, ICT and Future Planning | NRF-2014R1A1A3050645 |
| National Research Foundation of Korea |
Keywords
- cancer chemotherapy
- controlled release
- nanoparticles
- proteasome inhibitors
- solid cancers
ASJC Scopus subject areas
- Pharmaceutical Science
