HA Hydrogel Microspheres for Injectable Sustained Drug Release
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Solution Overview
Problem
Existing drug delivery systems face challenges in achieving sustained release of drugs, particularly for conformationally sensitive drugs like proteins or peptides, due to uncontrolled burst-type release and instability of the drug-hydrogel complex after administration, which can lead to dysfunctional drugs during the complexation process and instability of the drug-hydrogel complex after administration.
Innovation Solution
The method involves preparing hydrogel hydrogel microspheres or pharmaceutically acceptable salts thereof comprising a crosslinked hyaluronic acid (HA) by mixing a solution A with a solution B to form an emulsion, optionally adding a pH-adjusting agent to the emulsion, and collecting the obtained hydrogel hydrogel hydrogel microspheres or pharmaceutically acceptable salts thereof, which are used as carriers which are covalently conjugated to drug moieties and can provide a localized drug delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If non-covalent complexation is used to load drugs into hydrogel, then the drug can be embedded in the hydrogel, but uncontrolled burst-type release occurs due to disintegration of the drug-hydrogel complex after administration
Solution Approach 1:
The patent divides the drug delivery system into discrete microspheres (50-500 μm) rather than using bulk hydrogel. This segmentation allows the drug to be loaded into individual spherical carriers that maintain structural integrity after injection, preventing burst release while enabling controlled diffusion over time.
Solution Approach 2:
The patent creates composite hydrogel microspheres combining hyaluronic acid (HA) with crosslinking agents and drug moieties. The composite structure includes covalently bonded drug-linker-HA networks within the microsphere matrix, providing both stable drug loading and controlled release through the crosslinked gel network.
2Ease of manufacture
If conformationally sensitive drugs like proteins or peptides are complexed with hydrogel, then the drug can be delivered, but the drugs become dysfunctional during the complexation process and/or during subsequent storage
Solution Approach 1:
The patent replaces mechanical mixing and bulk hydrogel formation with suspension polymerization to create microspheres. This allows drug conjugation to occur during the gentle emulsification process rather than after complexation, reducing mechanical stress on conformationally sensitive drugs while maintaining stable drug-hydrogel complexes.
Solution Approach 2:
The patent performs preliminary drug conjugation to the hydrogel during the emulsion formation step before microsphere creation. By conjugating drugs to functionalized HA in solution before microsphere formation, the drugs are protected from conformational changes that would occur during subsequent storage and administration.
3Duration of action of moving object
If conventional bulk hydrogel is used for drug delivery, then the hydrogel can provide sustained release, but the injectability is poor and cannot pass easily through the needle
Solution Approach 1:
The patent segments bulk hydrogel into microspheres with controlled sizes (50-500 μm). This segmentation maintains the sustained release properties of hydrogel while enabling the microspheres to pass through needles and injection sites, as the smaller individual particles can navigate through narrow lumens without causing tissue damage.
Solution Approach 2:
The patent changes the physical parameters of hydrogel from bulk form to microsphere form with controlled size distribution. The microspheres are formed through suspension polymerization with specific monomer-to-monomer ratios and crosslinking conditions that create a porous gel structure maintaining sustained release while reducing individual particle size for improved injectability.
4Reliability
If crosslinked hyaluronic acid is used to form hydrogel microspheres, then the microspheres provide stable drug delivery, but the manufacturing process becomes more complex
Solution Approach 1:
The patent employs self-service crosslinking where functionalized HA molecules automatically crosslink with each other during emulsion formation. The first and second functionalized HA with complementary functional groups (-FG1 and -FG2) react spontaneously to form crosslinks, eliminating the need for external crosslinking agents or complex multi-step processes while achieving stable biostable microspheres.
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 enhances the injectability of the hydrogel microspheres or pharmaceutically acceptable salts thereof, which are used as carriers which are covalently conjugated to drug moieties and can provide a localized drug delivery.
Implementation Method 1
a first functionalized HA that is modified with one or more -FG1 and optionally further functional groups and a second functionalized HA that is modified with one or more -FG2 and optionally further functional groups, wherein each -FG1 and -FG2 are functional group moieties that are different from each other, wherein -FG1 on the first functionalized HA reacts with -FG2 on the second functionalized HA to form a plurality of crosslinks which results in the formation of hydrogel HA microspheres
Implementation Method 2
mixing a solution A with a solution B to form an emulsion
Data Source
AI summary
The present invention relates to hydrogel hyaluronic acid (HA) microspheres or pharmaceutically acceptable salts thereof that are prepared via suspension polymerization. Said hydrogel HA microspheres prepared according to the methods of the present invention may be used as carriers of various agents, such as carriers of various drug moieties. The present invention also provides for drug conjugates or pharmaceutically acceptable salts thereof that employ said hydrogel HA microspheres as carriers, methods of making said drug conjugates, pharmaceutical compositions comprising said drug conjugates and their use.