Hydrogel-Encapsulated Polypeptide Crystals for Low Viscosity High Loading
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Solution Overview
Problem
Current formulations of polypeptides, such as antibodies, face challenges in administration due to high viscosity and immunogenicity issues at high concentrations, leading to bioavailability and stability problems, and existing methods for improving flow properties are laborious and require repeated optimization for different polypeptides.
Innovation Solution
The use of hydrogels to encapsulate solid forms of polypeptides, such as crystalline antibodies, which results in compositions with high loadings and low viscosities, maintaining structural and functional stability for therapeutic and prophylactic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If polypeptides are administered at high concentrations to improve therapeutic efficacy, then the concentration of polypeptide in the composition is improved, but the viscosity of the composition increases and flow properties deteriorate
Solution Approach 1:
The patent changes the physical state parameter of the polypeptide from dissolved to solid form (crystals), which fundamentally alters the viscosity-concentration relationship. Solid polypeptide crystals maintain low composition viscosity even at high polypeptide loadings because they do not contribute to the liquid phase viscosity the way dissolved polypeptides do
Solution Approach 2:
The invention creates a composite composition combining solid polypeptide crystals with a liquid carrier matrix. This composite structure allows the polypeptide to be present at high concentrations while the liquid carrier maintains favorable flow properties, effectively decoupling the concentration-viscosity trade-off
2Quantity of substance
If polypeptides are administered at high concentrations to improve therapeutic efficacy, then the concentration of polypeptide in the composition is improved, but immunogenicity issues arise and stability problems occur
Solution Approach 1:
Changing the polypeptide from dissolved to crystalline solid form stabilizes its three-dimensional structure, protecting it from conformational changes, aggregation, and degradation. This crystalline state maintains biological activity and reduces immunogenicity even at high concentrations
Solution Approach 2:
The liquid carrier acts as an intermediary medium that allows high concentrations of stable crystalline polypeptide to be administered while maintaining acceptable flow properties. The carrier enables the therapeutic benefits of high concentration without the harmful effects of poor stability
3Ease of operation
If existing methods are used to improve flow properties of polypeptide compositions, then viscosity is reduced, but the methods are laborious and require repeated optimization
Solution Approach 1:
The invention identifies a fundamental parameter change - using solid crystalline form instead of dissolved state - that inherently provides good flow properties. This approach eliminates the need for laborious optimization of additives, buffers, and other formulation components that are typically required to manage viscosity
Solution Approach 2:
The patent adopts the successful formulation strategy from small molecule pharmaceuticals where crystalline solids are used, adapting this approach to polypeptide therapeutics. This copying of an established successful model simplifies the development process compared to traditional polypeptide formulation approaches
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The hydrogel-encapsulated solid forms of polypeptides provide stable, concentrated formulations with improved flow properties and extended shelf life, allowing for convenient and less invasive administration while maintaining biological activity and stability.
Implementation Method 1
The compositions may include carriers such as hydrogels that at least partially encapsulate the solid form of the polypeptides (e.g., crystals, amorphous solids)
Implementation Method 2
the hydrogel comprises covalently cross-linked polymer chains, ionically cross-linked polymer chains, and/or thermally cross-linked polymer chains
Data Source
AI summary
Compositions including solid forms of polypeptides such as crystalline antibodies, and related methods, are generally described. The compositions may include carriers such as hydrogels that at least partially encapsulate the solid form of the polypeptides (e.g., crystals, amorphous solids). Encapsulation with certain of the materials described may result in compositions containing relatively high loadings of polypeptides while in some instances retaining structural and functional properties of the polypeptides useful for certain types of administration to subjects (e.g., for prophylactic or therapeutic applications). In some instances, compositions having relatively low dynamic viscosities while having relatively high polypeptide loadings are provided.