Poloxamer-Protein Particles for Sustained Release
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Solution Overview
Problem
Protein delivery from PLGA microparticles faces challenges due to protein stability issues during formulation and release, leading to incomplete and unstable release profiles, with a common problem being the 'burst effect' and instability caused by moisture-induced aggregation and ionic interactions.
Innovation Solution
A method involving the precipitation of proteins with poloxamers to form poloxamer-protein particles, which are then encapsulated, allowing for a controlled and sustained release of proteins over 20 days without the need for stabilizing agents like albumin or trehalose, utilizing a s/o/w method or prilling, and using glycofurol as a water-miscible non-solvent to induce precipitation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If protein is delivered from PLGA microparticles, then sustained release is achieved, but protein stability deteriorates due to moisture-induced aggregation and ionic interactions
Solution Approach 1:
Poloxamer acts as an intermediary substance between the protein and PLGA polymer matrix. The poloxamer forms a protective complex with the protein during encapsulation, preventing direct contact between the protein and the hydrophobic PLGA matrix, thereby preventing aggregation and degradation while enabling sustained release over 20 days
Solution Approach 2:
The invention uses a composite formulation consisting of PLGA polymer matrix combined with poloxamer surfactant. This composite material system provides both the sustained release capability of PLGA and the protein stabilization function of poloxamer, resolving the contradiction between release duration and protein stability
2Reliability
If stabilizing additives are used to minimize protein degradation, then protein stability improves, but release completeness deteriorates because stabilizers diffuse rapidly from microparticles
Solution Approach 1:
The invention merges the stabilizing function with the release mechanism by forming a poloxamer-protein complex that is co-encapsulated within the PLGA matrix. This integrated approach ensures that the stabilizing poloxamer remains associated with the protein throughout the entire release period, preventing the rapid diffusion problem that plagues conventional stabilizer approaches and enabling complete release
3Duration of action of moving object
If protein is encapsulated in PLGA microparticles, then sustained release is achieved, but burst effect occurs leading to incomplete release
Solution Approach 1:
Poloxamer serves as a mediating agent that modifies the interface between protein and PLGA matrix, creating a more uniform distribution and preventing the rapid initial release characteristic of burst effect. The poloxamer-protein complex integrates more smoothly into the polymer matrix, enabling controlled sustained release without the initial massive release that compromises completeness
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 ensures complete and continuous release of proteins in a biologically active form, avoiding the burst effect and maintaining protein stability during the release period, with improved release profiles and high yields applicable to a wide range of proteins.
Implementation Method 1
when the protein was precipitated in the presence of a poloxamer, particles of protein/poloxamer were formed
Implementation Method 2
contacting the obtained solution with a water-miscible protein non sovent which is glycofurol, with a volume ratio of glycofurol/aqueous solution ranging from 5 to 100, to form a dispersion of poloxamer-protein particles
Implementation Method 3
As poloxamer is a surfactant, it is assumed that its presence limits the interactions between the protein and the polymer which encapsulates the protein
Data Source
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AI summary
The present invention relates to a method for preparing poloxamer-protein particles. It also relates to poloxamer-protein particles obtainable by this method, dispersion thereof, and their use in methods of encapsulation, in particular of microencapsulation.