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Overcoming intestinal barriers by heparanase-responsive charge-converting nanocarriers
Florina Veider1, Katrin Zöller1, Ahmad Saleh2
1Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
International Journal of Pharmaceutics
|January 18, 2024
Summary
Novel nanocarriers (NCs) overcome intestinal barriers by converting charge in response to heparanase (HPSE). This strategy significantly enhances mucus penetration and cellular uptake for targeted drug delivery applications.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery
Background:
- Intestinal barriers limit drug absorption.
- Heparanase (HPSE) is overexpressed in cancer cells.
- Targeted delivery systems are needed to overcome these barriers.
Purpose of the Study:
- To develop heparanase-responsive charge-converting nanocarriers (NCs) for enhanced intestinal barrier penetration.
- To evaluate the efficacy of these NCs in improving cellular uptake in vitro.
Main Methods:
- Heparin-coated nanostructured lipid carriers (NLCs) and solid lipid nanocarriers (SLNs) were synthesized.
- Charge conversion was induced by enzymatic cleavage of heparin by heparanase.
- Mucus permeation and cellular uptake were assessed using in vitro models (HT29, Caco-2 cells).
Main Results:
- Heparin-coated NCs exhibited a significant shift in zeta potential upon exposure to heparanase.
- Mucus permeation was improved more than 6-fold compared to uncoated NCs.
- Cellular uptake was enhanced up to 4-fold in heparanase-expressing cancer cells.
Conclusions:
- Heparanase-responsive charge-converting NCs offer a promising strategy for overcoming intestinal barriers.
- This approach enhances drug delivery and cellular uptake in targeted cancer cells.
- Further research into these NCs could advance intestinal drug delivery systems.
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