Sustained delivery of anti-VEGF from injectable hydrogel systems provides a prolonged decrease of endothelial cell
Nathan A Fletcher1, Melissa D Krebs1
1Department of Chemical and Biological Engineering, Colorado School of Mines 1613 Illinois Street Golden CO 80401 USA mdkrebs@mines.edu.
RSC Advances
|May 11, 2022
Summary
This study developed an alginate-chitosan polyelectrolyte complex (PEC) for sustained 30-day delivery of therapeutic antibodies. The system successfully released anti-VEGF antibodies, inhibiting angiogenesis in vitro.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Immunology
Background:
- Therapeutic antibodies offer targeted treatment for diseases by binding specific antigens.
- Bevacizumab, an anti-VEGF antibody, is promising for cancers and macular degeneration, conditions linked to aberrant angiogenesis.
- Local, sustained antibody delivery can enhance efficacy, reduce dosing frequency, and minimize systemic side effects.
Purpose of the Study:
- To design and evaluate an alginate-chitosan polyelectrolyte complex (PEC) for controlled, 30-day local delivery of therapeutic antibodies.
- To investigate the release kinetics of different antibodies from the PEC system.
- To assess the in vitro efficacy of released anti-VEGF antibodies in inhibiting angiogenesis.
Main Methods:
- Fabrication of an alginate-chitosan polyelectrolyte complex (PEC) as a carrier for antibodies.
- Encapsulation and evaluation of 30-day release profiles for non-specific IgG and anti-VEGF antibodies.
- In vitro assessment of the biological activity of released anti-VEGF antibodies on VEGF-induced proliferation and angiogenesis.
Main Results:
- The alginate-chitosan PEC system demonstrated sustained release of antibodies over a 30-day period.
- Release rates were antibody-specific, with anti-VEGF showing slower release compared to IgG, attributed to PEC-antibody charge interactions.
- Released anti-VEGF antibodies effectively inhibited VEGF-induced proliferation and angiogenesis in vitro.
Conclusions:
- Alginate-chitosan PECs are a viable system for sustained, localized delivery of therapeutic antibodies.
- The system offers potential for improved treatment of angiogenesis-related diseases by providing prolonged therapeutic antibody levels at the target site.
- Antibody-specific release characteristics from PECs can be leveraged for tailored drug delivery strategies.
Related Concept Videos
Regulation of Angiogenesis and Blood Supply
2.8K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.8K
Mechanism of Angiogenesis
6.0K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.0K


