Uncapped PLGA Microparticles for Stable Protein Encapsulation
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Solution Overview
Problem
Conventional encapsulation methods for therapeutic agents in biodegradable polymers face challenges such as destabilization of proteins and peptides, low loading efficiency, high manufacturing costs, and difficulty in manipulating release kinetics, particularly for self-antigens used in autoimmune disease treatment.
Innovation Solution
The use of uncapped PLGA or PLA polymers with free carboxyl groups and positively charged therapeutic agents, coupled with counter ions, allows for high encapsulation efficiency and controlled release of therapeutic agents, minimizing exposure to harsh solvents and agitation, and enabling sustained delivery of self-antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional encapsulation methods using organic solvents, high temperatures, and homogenization are employed, then therapeutic agents can be encapsulated in biodegradable polymers, but the therapeutic agents (particularly proteins and peptides) become destabilized and loading efficiency decreases
Solution Approach 1:
The patent changes the physical and chemical parameters of the encapsulation process by using aqueous solutions instead of organic solvents, maintaining physiological temperatures instead of high temperatures, and eliminating mechanical homogenization. These parameter changes create a gentle environment that preserves therapeutic agent stability while achieving effective encapsulation in biodegradable polymers
Solution Approach 2:
The patent introduces an intermediary mechanism where biodegradable polymer particles serve as a protective carrier that gradually releases therapeutic agents. The polymer matrix acts as an intermediary between the therapeutic agent and the external environment, protecting sensitive proteins and peptides from destabilizing conditions while enabling controlled delivery
2Quantity of substance
If high concentrations of drug dissolved in water or acetic acid are used for encapsulation, then loading efficiency improves, but the drug becomes destabilized or solubility limits are exceeded
Solution Approach 1:
The patent changes the solvent parameter from organic solvents (acetic acid) or pure water to aqueous buffer solutions with controlled pH and ionic strength. This parameter change enables dissolution of drugs at high concentrations while maintaining drug stability through buffered conditions that prevent denaturation and aggregation
Solution Approach 2:
The patent uses composite material systems combining biodegradable polymers with aqueous buffer solutions containing therapeutic agents. The polymer matrix composite structure allows high drug loading concentrations to be achieved within the particle formulation while the aqueous environment maintains drug stability, overcoming the solubility-stability trade-off
3Shape
If micronization of therapeutic agent is performed prior to encapsulation, then particle size control improves, but the therapeutic agent becomes further destabilized
Solution Approach 1:
The patent reverses the conventional sequence by performing encapsulation first and particle size control second. The therapeutic agent is encapsulated in its native, stable form within the polymer matrix, and particle size is subsequently controlled through controlled polymer degradation. This preliminary encapsulation action protects the agent from destabilizing size-reduction processes
4Reliability
If conventional encapsulation methods are used, then therapeutic agents can be delivered, but manufacturing costs become high due to aseptic processing requirements
Solution Approach 1:
The patent changes the processing parameters to aqueous-based, low-temperature, non-sterile conditions that are compatible with standard manufacturing equipment. This eliminates the need for expensive aseptic processing facilities and validation while maintaining therapeutic agent integrity, thereby reducing manufacturing costs
Solution Approach 2:
The patent employs disposable, biodegradable polymer particles that can be manufactured using simple, low-cost processes. The particles are designed for single-use injection, eliminating the need for complex sterilization and storage infrastructure, thereby reducing overall manufacturing and distribution costs
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 (>60%) and high drug loading (>5% w/w) with controlled release, maintaining therapeutic agent stability and reducing manufacturing costs, while providing sustained delivery of self-antigens for autoimmune disease treatment.
Implementation Method 1
the uncapped polymer comprises free carboxyl groups at the end of the polymer... therapeutic agent associated with and distributed in and encapsulated by the polymer matrix, wherein the therapeutic agent is net positively charged at neutral pH
Implementation Method 2
Injectable, biodegradable polymeric particles... can release the therapeutic agent over the course of hours, days or more extended periods such as weeks or months
Data Source
AI summary
The disclosure relates to microparticles and nanoparticles comprising a polymer matrix comprising an uncapped polymer and a net positively charged therapeutic agent at neutral pH. More particularly the disclosure relates to PLGA and/or PLA particles comprising an uncapped polymer for extended, controlled release of positively charged proteins or peptides at neutral pH. Methods of making the particles and administering the particles are also provided.