Replenishable drug depot to combat post-resection cancer recurrence

Yevgeny Brudno; Matthew J Pezone; Tracy K Snyder; Oktay Uzun; Christopher T Moody; Michael Aizenberg; David J Mooney

doi:10.1016/j.biomaterials.2018.05.005

Replenishable drug depot to combat post-resection cancer recurrence

Biomaterials. 2018 Sep:178:373-382. doi: 10.1016/j.biomaterials.2018.05.005. Epub 2018 May 6.

Authors

Yevgeny Brudno¹, Matthew J Pezone², Tracy K Snyder², Oktay Uzun², Christopher T Moody³, Michael Aizenberg², David J Mooney⁴

Affiliations

¹ Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Cir., Boston, MA 02115, USA; School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA; Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, 911 Oval Drive, Raleigh, NC 27695, USA; Lineberger Comprehensive Cancer Center, University of North Carolina - Chapel Hill, 450 West Dr, Chapel Hill, NC 27599, USA.
² Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Cir., Boston, MA 02115, USA.
³ Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, 911 Oval Drive, Raleigh, NC 27695, USA.
⁴ Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Cir., Boston, MA 02115, USA; School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA. Electronic address: mooneyd@seas.harvard.edu.

Abstract

Local drug presentation made possible by drug-eluting depots has demonstrated benefits in a vast array of diseases, including in cancer, microbial infection and in wound healing. However, locally-eluting depots are single-use systems that cannot be refilled or reused after implantation at inaccessible sites, limiting their clinical utility. New strategies to noninvasively refill drug-eluting depots could dramatically enhance their clinical use. In this report we present a refillable hydrogel depot system based on bioorthogonal click chemistry. The click-modified hydrogel depots capture prodrug refills from the blood and subsequently release active drugs locally in a sustained manner. Capture of the systemically-administered refills serves as an efficient and non-toxic method to repeatedly refill depots. Refillable depots in combination with prodrug refills achieve sustained release at precancerous tumor sites to improve cancer therapy while eliminating systemic side effects. The ability to target tissues without enhanced permeability could allow the use of refillable depots in cancer and many other medical applications.

Keywords: Biomaterials; Cancer therapy; Drug delivery; Drug depot; Sustained release.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alginates / chemistry
Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Cell Proliferation / drug effects
Click Chemistry
Doxorubicin / chemistry
Doxorubicin / pharmacology
Doxorubicin / therapeutic use
Female
Hydrogels / chemistry
Kinetics
Mice
Neoplasm Recurrence, Local / drug therapy*
Neoplasm Recurrence, Local / pathology
Neoplasms / pathology
Neoplasms / surgery*
Prodrugs / chemical synthesis
Prodrugs / pharmacology
Prodrugs / therapeutic use
Prodrugs / toxicity
Subcutaneous Tissue / drug effects

Substances

Alginates
Antineoplastic Agents
Hydrogels
Prodrugs
Doxorubicin

Abstract

Publication types

MeSH terms

Substances

Grants and funding