Kathryn M Camacho1, Stefano Menegatti2, Samir Mitragotri1. 1. Department of Chemical Engineering, Center for Bioengineering, University of California at Santa Barbara, Santa Barbara, CA 93106, USA. 2. Department of Chemical & Biomolecular Engineering, Department of Biomedical Engineering, Biomanufacturing Training and Education Center (BTEC), North Carolina State University, Raleigh, NC 27695, USA.
Abstract
BACKGROUND: High-molecular-weight (MW) polymers (>50,000 Da) can be conjugated to chemotherapy drugs in order to improve their tumor accumulation, while low MW polymers ≤10,000 Da are often overlooked due to faster plasma clearance. Small polymers, however, may facilitate deeper tumor penetration. MATERIALS & METHODS: Here, we investigate the anticancer efficacy of 10 kDa hyaluronic acid or poly(vinyl alcohol) conjugated to synergistic combinations of camptothecin and doxorubicin, with emphasis on chemical linker impacts. RESULTS: Our results emphasize drug hydrolyzability for synergy preservation, and also demonstrate superior cancer cell inhibition with low MW polymer-drug conjugates. CONCLUSION: This study shows the high therapeutic potential of low MW polymer-drug conjugates for polychemotherapy delivery, and provides further insight into the development of polymer-drug therapeutics.
BACKGROUND: High-molecular-weight (MW) polymers (>50,000 Da) can be conjugated to chemotherapy drugs in order to improve their tumor accumulation, while low MW polymers ≤10,000 Da are often overlooked due to faster plasma clearance. Small polymers, however, may facilitate deeper tumor penetration. MATERIALS & METHODS: Here, we investigate the anticancer efficacy of 10 kDa hyaluronic acid or poly(vinyl alcohol) conjugated to synergistic combinations of camptothecin and doxorubicin, with emphasis on chemical linker impacts. RESULTS: Our results emphasize drug hydrolyzability for synergy preservation, and also demonstrate superior cancer cell inhibition with low MW polymer-drug conjugates. CONCLUSION: This study shows the high therapeutic potential of low MW polymer-drug conjugates for polychemotherapy delivery, and provides further insight into the development of polymer-drug therapeutics.
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