Pore-Closing Polymer Encapsulation for Biomacromolecules

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Solution Overview

Problem

Current methods for encapsulating biomacromolecules in biodegradable polymers, such as PLGA microspheres, often require harsh processing conditions that can denature proteins and destabilize other biomolecules, and fail to achieve stable, controlled release due to instability during encapsulation and in vivo release.

Innovation Solution

A method involving the use of a pore-containing polymer where biomacromolecules are allowed to enter the pores of preformed microspheres or scaffolds, followed by pore closure through temperature, pH, or additive manipulation, eliminating the need for organic solvents, micronization, and drying, and enabling terminal sterilization and point-of-care microencapsulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional encapsulation methods using organic solvents and harsh processing conditions are used, then encapsulation efficiency can be achieved, but biomacromolecules are denatured and destabilized

Engineering Contradiction:
Improveencapsulation efficiencyVSAvoidbiomacromolecule stability
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent changes the physical and chemical parameters of the polymer system by introducing pore-containing polymers with specific pore sizes and distributions. This allows encapsulation to occur under milder conditions by utilizing the pore structure to trap biomacromolecules without requiring harsh solvents or processing, thereby maintaining biomacromolecule stability while achieving efficient encapsulation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs pore-containing polymers as the encapsulation matrix. The porous structure provides physical entrapment sites for biomacromolecules, enabling encapsulation without the need for organic solvents or extreme processing conditions. The pores allow biomacromolecules to be trapped in their native state, preventing denaturation while achieving high encapsulation efficiency

Inventive Principle:
Principle #31Porous materials

2Ease of manufacture

If micronization and drying of biomacromolecules are performed before encapsulation, then encapsulation process can be simplified, but biomacromolecules are further destabilized

Engineering Contradiction:
Improveencapsulation process simplicityVSAvoidbiomacromolecule stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent performs preliminary preparation of the polymer matrix by creating pore-containing structures before introducing the biomacromolecules. This preliminary action of preparing the encapsulation matrix with appropriate pore structure allows direct encapsulation of biomacromolecules in solution form, eliminating the need for subsequent micronization and drying steps that would destabilize the biomacromolecules

Inventive Principle:
Principle #10Preliminary action

3Duration of action of moving object

If protein release occurs through diffusion through polymer phase, then controlled release can be achieved, but release is unstable and incomplete due to protein instability

Engineering Contradiction:
Improverelease durationVSAvoidrelease stability
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The patent uses pore-containing polymers where the porous structure provides stable diffusion pathways for protein release. The pores maintain their structure throughout the release process, ensuring consistent and reliable protein diffusion. This porous architecture allows complete and stable release of proteins over extended periods, overcoming the instability issues associated with dense polymer matrices

Inventive Principle:
Principle #31Porous materials

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

This method achieves high encapsulation efficiency (>10%) without denaturing biomolecules, allows for controlled release profiles, and is applicable to various biomaterials, reducing costs and improving the stability of protein and nucleic acid drugs.

Implementation Method 1

contacting the biomacromolecule with the pore-containing polymer for a time sufficient for the biomacromolecule to enter the pores of the pore-containing polymer

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

closing the pores of the pore-containing polymer wherein the biomacromolecules is encapsulated in the pore-containing polymer

Methodology Applied
Scientific EffectPhase change: Phase Change

Data Source

PatentUS8017155B2Methods for encapsulation of biomacromolecules in polymers
Publication Date: 2011.09.13 THE RGT UNIV OF MICHIGAN
  • US8017155B2 patent drawing
  • US8017155B2 patent drawing
  • US8017155B2 patent drawing

AI summary

A method for encapsulating a biomacromolecule in a pore-containing polymer comprising the steps of providing an encapsulating solution containing the biomacromolecule and the pore-containing polymer; contacting the biomacromolecule with the pore-containing polymer for a time sufficient for the biomacromolecule to enter the pores of the pore-containing polymer; and rearranging the polymer such that the surface pores of the polymer are closed thus encapsulating the biomacromolecule in the pore-containing polymer.