Hydrogel vehicles for sequential delivery of protein drugs to promote vascular regeneration

Zhao Wei; Eugenia Volkova; Michael R Blatchley; Sharon Gerecht

doi:10.1016/j.addr.2019.08.005

Hydrogel vehicles for sequential delivery of protein drugs to promote vascular regeneration

Adv Drug Deliv Rev. 2019 Sep-Oct:149-150:95-106. doi: 10.1016/j.addr.2019.08.005. Epub 2019 Aug 14.

Authors

Zhao Wei¹, Eugenia Volkova¹, Michael R Blatchley², Sharon Gerecht³

Affiliations

¹ Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.
² Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: gerecht@jhu.edu.

Abstract

In recent years, as the mechanisms of vasculogenesis and angiogenesis have been uncovered, the functions of various pro-angiogenic growth factors (GFs) and cytokines have been identified. Therefore, therapeutic angiogenesis, by delivery of GFs, has been sought as a treatment for many vascular diseases. However, direct injection of these protein drugs has proven to have limited clinical success due to their short half-lives and systemic off-target effects. To overcome this, hydrogel carriers have been developed to conjugate single or multiple GFs with controllable, sustained, and localized delivery. However, these attempts have failed to account for the temporal complexity of natural angiogenic pathways, resulting in limited therapeutic effects. Recently, the emerging ideas of optimal sequential delivery of multiple GFs have been suggested to better mimic the biological processes and to enhance therapeutic angiogenesis. Incorporating sequential release into drug delivery platforms will likely promote the formation of neovasculature and generate vast therapeutic potential.

Keywords: Angiogenesis; Growth factors; Hydrogel carriers; Sequential release.

Publication types

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

MeSH terms

Animals
Drug Carriers / administration & dosage
Drug Carriers / chemistry
Drug Delivery Systems*
Humans
Hydrogels / administration & dosage*
Hydrogels / chemistry
Neovascularization, Physiologic / drug effects*
Vascular Endothelial Growth Factors / metabolism

Substances

Drug Carriers
Hydrogels
Vascular Endothelial Growth Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding