pH-responsive hydrogel technology for enhanced oral delivery of therapeutic proteins

Improved hydrogel copolymers, made from itaconic acid and N-vinylpyrrolidone, enable oral delivery of therapeutic proteins by protecting them in the stomach and releasing them in the intestine. This enhances protein bioavailability and pharmacokinetics.

Background

Oral delivery of therapeutic proteins presents significant challenges due to the body’s natural mechanisms for breaking down proteins in the gastrointestinal tract. Proteins must survive the acidic and proteolytic environment of the stomach and remain stable in the neutral pH of the small intestine to be effectively absorbed into the bloodstream. Traditional methods often result in low bioavailability, as proteins are degraded before they can be absorbed, necessitating alternative delivery strategies.

pH-sensitive hydrogels have been explored to protect proteins during transit through the stomach and facilitate release in the intestine. However, these systems often suffer from limited effectiveness due to inadequate protection or release mechanisms, particularly for proteins with high isoelectric points, which can interact unfavorably with the hydrogel matrix. Additionally, existing hydrogels may not swell sufficiently or quickly enough in the intestinal environment to release the protein payload effectively, leading to wasted drug and increased costs. These challenges highlight the need for improved hydrogel systems that can enhance the loading, protection, and release of therapeutic proteins for oral administration.

Technology description

Improved hydrogel copolymers, composed of itaconic acid and N-vinylpyrrolidone, are engineered for the oral delivery of therapeutic proteins, particularly those with high isoelectric points. These copolymers are designed to swell in response to pH changes, allowing them to protect proteins in the acidic environment of the stomach and release them in the neutral pH of the small intestine. The loading of proteins into these hydrogels is optimized using a reduced ionic strength solution, which enhances the copolymer’s ability to load and release proteins effectively.

This method improves the pharmacokinetic properties of the protein-hydrogel compositions, potentially increasing the bioavailability of orally administered therapeutic proteins. The copolymers can be crosslinked using agents like tetra(ethylene glycol)dimethacrylate to adjust their mechanical properties and swelling behavior, making them suitable for delivering a range of protein therapeutics.

This technology is differentiated by its use of itaconic acid, which provides superior swelling behavior compared to traditional methacrylic acid-based hydrogels. The dual carboxylic acid groups in itaconic acid allow for greater and faster pH-responsive swelling, which is crucial for timely protein release in the small intestine. Additionally, the use of reduced ionic strength solutions during protein loading enhances the copolymers' ability to encapsulate and subsequently release proteins, addressing a significant challenge in oral protein delivery. This approach not only improves the delivery potential but also reduces drug waste, making it a cost-effective solution. The ability to tailor the copolymers' mechanical and swelling properties through crosslinking further enhances their versatility, allowing for the delivery of a wide range of therapeutic proteins with varying molecular sizes and isoelectric points.

Benefits

Enhanced bioavailability of orally administered therapeutic proteins
Protection of proteins in the acidic environment of the stomach and release in the neutral pH of the small intestine
Improved pharmacokinetic properties of protein-hydrogel compositions
Adjustable mechanical properties and swelling behavior for delivering a range of protein therapeutics
Ability to deliver high isoelectric point proteins effectively
Potential for increased patient compliance
Improved patient’s quality of life by avoiding injections
Reduced cost compared to injectable forms