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Hydrophobic Tags for Highly Efficient Light-Activated Protein Release
Karthik Nadendla1, Bhagyesh R Sarode1, Simon H Friedman1
1Division of Pharmaceutical Sciences , University of Missouri-Kansas City, School of Pharmacy , Kansas City , Missouri 64108 , United States.
Molecular Pharmaceutics
|May 24, 2019
Summary
New hydrophobic tags enable photoactivated depot (PAD) systems for controlled insulin release. This approach improves insulin concentration and eliminates polymer biodegradation for better therapeutic protein delivery.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Protein Engineering
Background:
- The photoactivated depot (PAD) approach enables light-stimulated release of therapeutic proteins like insulin.
- Previous PAD methods used polymer beads, leading to low insulin concentration and biodegradation issues.
Purpose of the Study:
- To develop an improved PAD system for insulin delivery using photocleavable hydrophobic tags.
- To overcome limitations of polymer-based depots, enhancing insulin concentration and eliminating the need for biodegradation.
Main Methods:
- Synthesized insulin modified with photocleavable hydrophobic tags using a combined solid- and solution-phase approach.
- Characterized the resulting insulin materials for solubility, particle size, and injectability.
- Demonstrated light-stimulated release of soluble, native insulin from the depot.
Main Results:
- Developed insulin materials with >90% w/w insulin content and significantly reduced solubility (≤1000× lower).
- Created injectable micron-sized particles suitable for delivery via a 31G needle.
- Achieved effective insulin suspension concentrations (20 mM) for sustained, 7-day delivery.
Conclusions:
- Hydrophobic tags offer a superior alternative to polymers for PAD systems, enhancing insulin loading and simplifying clearance.
- The developed modified insulins are highly suitable candidates for advanced photoactivated depot applications.
- This technology promises improved controlled release of therapeutic proteins.
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