Polymer-Coated Protein Microparticles for Sustained Ocular Release
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a significant unmet medical need for extended release formulations of protein therapeutics that can deliver therapeutic proteins effectively over time with minimal intraocular injections for conditions such as ocular diseases, and improved implantable formulations for diseases like cancer and inflammation, where existing technologies do not provide sustained and uniform release.
Innovation Solution
The development of biodegradable polymer-coated protein microspheres, specifically using polyorthoester (POE), polylactic acid (PLA), and poly-D,L-lactide-co-glycolide (PLGA) to create microparticles with a protein core coated in a polymer cortex, allowing for controlled and uniform release of therapeutic proteins over an extended period.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional delivery methods are used, then the therapeutic protein can be administered, but the duration of action is short and requires frequent intraocular injections
Solution Approach 1:
The therapeutic protein is segmented into multiple microparticles, each containing a small amount of protein encapsulated within biodegradable polymer shells. This segmentation allows the protein to be distributed across many particles that collectively provide sustained release over extended periods, reducing the need for frequent injections while maintaining therapeutic efficacy.
Solution Approach 2:
Biodegradable polymer shells form flexible, thin-film encapsulations around the therapeutic protein. These polymer matrices degrade slowly over time, providing controlled release of the protein while protecting it from degradation. The flexible polymer structure allows for sustained delivery over months, significantly extending the duration of action compared to conventional injection methods.
2Duration of action of moving object
If the polymer cortex is made thicker to extend release duration, then the release period is prolonged, but the manufacturing precision and uniformity of protein release may be compromised
Solution Approach 1:
The invention employs precise control of polymerization parameters, crosslinking density, and polymer composition to achieve consistent microparticle properties. By optimizing parameters such as polymer molecular weight, degradation rate, and cortex thickness distribution, the system achieves both extended release duration and uniform protein release kinetics across the microparticle population.
Solution Approach 2:
The microparticles utilize composite structures combining biodegradable polymers with controlled crosslinking agents and potentially multiple polymer layers. This composite approach allows fine-tuning of the release profile by adjusting the composition and architecture of the polymer matrix, achieving both prolonged duration and uniform release characteristics that neither simple polymer alone could provide.
3Duration of action of moving object
If existing extended release formulations are used, then some duration extension is achieved, but uniform and sustained release over 60+ days is not maintained
Solution Approach 1:
The microparticle design incorporates feedback mechanisms where the polymer degradation rate is coupled with protein release kinetics. As the polymer matrix degrades, it progressively releases the encapsulated protein in a controlled manner, with the degradation products potentially influencing further release rates. This self-regulating feedback ensures consistent, sustained release over 60+ days without deviation from the desired release profile.
Solution Approach 2:
The invention utilizes precise control of multiple parameters including polymer crosslinking density, mesh size, hydrophobicity, and degradation kinetics to achieve reliable, consistent release. By systematically optimizing these parameters, the system maintains uniform release rates over extended periods, ensuring therapeutic protein is delivered consistently throughout the 60-day period and beyond.
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
These microspheres enable a steady and prolonged release of therapeutic proteins, maintaining protein stability and efficacy for at least 60 days, reducing the frequency of injections and providing consistent delivery of proteins like VEGF-Trap for ocular and other conditions.
Implementation Method 1
Biocompatible and biodegradable polymers for the controlled and extended delivery of drugs have been in use for decades. As the polymer degrades over time, the therapeutic drug is slowly released.
Implementation Method 2
spray drying an aqueous therapeutic protein solution to form micronized therapeutic protein particles wherein the inlet temperature of the spray dryer is set at a temperature greater than the boiling point of water and the outlet temperature that is above ambient and below the boiling point of water
Implementation Method 3
spray drying the suspension to form the extended release pharmaceutical composition comprising a population of POE-coated therapeutic protein microparticles
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to microparticles comprising a protein particle core coated with a biodegradable polymer cortex, methods of manufacturing such microparticles, and methods for modulating the release of a protein. The microparticles are used in extended release pharmaceutical formulations for use in the vitreous for the treatment of vascular eye disorders.