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Published on: November 9, 2020
The impact of enzymatic degradation on the uptake of differently sized therapeutic molecules
Arne Erikson1, Ingunn Tufto, Anne Berit Bjønnum
1Department of Physics, Norwegian University of Science and Technology, H-gskoleringen 5, 7491 Trondheim.
Background:
The extracellular matrix represents a major barrier for drug delivery. This work compares the effects of collagenase and hyaluronidase on tumour uptake and distribution of two differently sized therapeutic molecules, IgG and liposomal doxorubicin.
Materials And Methods:
The enzymes were injected i.v. prior to the therapeutic molecules, and uptake and distribution were studied by confocal laser scanning microscopy. The therapeutic molecules were colocalized with the vasculature and collagen network visualized by the second harmonic signal.
Results:
Hyaluronidase increased the uptake of liposomal doxorubicin to a small extent, whereas collagenase had no effect. Collagenase increased, but hyaluronidase reduced the uptake of IgG. Neither of the enzymes induced changes in the collagen network measured by the second harmonic signal.
Conclusion:
Degradation of the collagen network improves delivery of molecules with the size of IgG, whereas degradation of the gel of glycosaminoglycans has a higher impact on the distribution of small drugs such as doxorubicin.
Insights
Enzyme treatment of the extracellular matrix impacts drug delivery differently. Collagenase aids IgG delivery, while hyaluronidase benefits liposomal doxorubicin, affecting tumor uptake and distribution.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Extracellular Matrix Research
Background:
- The extracellular matrix (ECM) poses a significant challenge for effective drug delivery.
- Understanding ECM components is crucial for optimizing therapeutic molecule transport.
Purpose of the Study:
- To investigate the impact of collagenase and hyaluronidase on the tumor uptake and distribution of IgG and liposomal doxorubicin.
- To evaluate the role of ECM-degrading enzymes in enhancing drug delivery.
Main Methods:
- Intravenous injection of collagenase and hyaluronidase prior to therapeutic molecules.
- Confocal laser scanning microscopy to assess uptake and distribution.
- Second harmonic generation imaging to visualize collagen network and vasculature.
Main Results:
- Hyaluronidase slightly enhanced liposomal doxorubicin uptake; collagenase had no effect.
- Collagenase increased IgG uptake, while hyaluronidase decreased it.
- Neither enzyme altered the collagen network structure.
Conclusions:
- Degrading the collagen network improves delivery for larger molecules like IgG.
- Degrading glycosaminoglycan-rich gels significantly impacts the distribution of smaller drugs, such as doxorubicin.
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