Brush Polymer Therapeutic Agents for Peptide Stability
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Solution Overview
Problem
Current peptide therapeutics face inefficiencies in cellular uptake and rapid degradation by proteases, limiting their clinical adoption due to poor in vivo stability, which restricts administration routes and patient compliance.
Innovation Solution
Development of brush polymer therapeutic agents with high brush densities, incorporating therapeutic peptides as side chain moieties, which are resistant to proteolysis and have enhanced circulation times, allowing for more versatile administration routes and reduced dosing frequencies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptide therapeutics are administered conventionally, then they can be delivered to target sites, but they undergo rapid degradation by proteases and have poor in vivo stability
Solution Approach 1:
The patent applies composite materials by conjugating therapeutic peptides with brush polymer carriers to create a hybrid structure that combines the biological activity of peptides with the stability and circulation time of synthetic polymers. This composite approach protects the peptide from proteolytic degradation while maintaining its therapeutic function, directly resolving the contradiction between in vivo stability and circulation duration
Solution Approach 2:
The patent changes the molecular weight parameter by attaching peptides to high molecular weight brush polymers, transforming the peptide from a small, rapidly cleared molecule to a larger conjugate with extended circulation time. This parameter change in molecular size and structure directly addresses the stability-duration contradiction
2Reliability
If chemical modification of amino acid sequence is used to protect peptides from proteolysis, then protease resistance is improved, but multiple rounds of structure-function studies are required to confirm activity is not altered
Solution Approach 1:
The patent introduces a brush polymer carrier as an intermediary between the peptide and the proteolytic environment. This mediator physically protects the peptide sequence from protease access without requiring chemical modification of the amino acids themselves, thereby maintaining original peptide activity while providing protease resistance and eliminating the need for extensive structure-function studies
3Reliability
If peptides are conjugated to pre-formed higher molecular weight structures, then proteolysis resistance is improved, but additional conjugation and purification steps are required
Solution Approach 1:
The patent segments the therapeutic agent into two functional components: the brush polymer carrier and the therapeutic peptide. This segmentation allows for independent optimization and characterization of each component before conjugation, simplifying the overall manufacturing process. The modular approach enables easier purification and quality control compared to forming complex high molecular weight carriers de novo
Data Source
AI summary
In an aspect, the invention provides therapeutic agents comprising brush polymers that address challenges associated with conventional administration of free therapeutic peptides. In an embodiment, for example, the invention provides brush polymers incorporating one or more therapeutic peptides as side chain moieties. Therapeutic agents of the invention comprising brush polymers include high-density brush polymers including cross-linked brush polymers and brush block copolymers. In an embodiment, brush polymers of the invention exhibit proteolysis-resistant characteristics and maintain their biological function during formulation and administration. The invention also includes methods of making and using therapeutic agents comprising brush polymers.