In Situ Crosslinked Hydrogel for Controlled Drug Release
Solution Overview
Problem
Current treatments for back-of-the-eye diseases such as age-related macular degeneration, diabetic retinopathy, and posterior uveitis face challenges with drug delivery, including inflammation, limited bioavailability, and the need for frequent intravitreal injections, which can cause side effects like cataracts and retinal detachments.
Innovation Solution
A crosslinked hydrogel is formed in situ within the eye using biocompatible precursors that release therapeutic agents over time, adhering to tissues, degrading into non-inflammatory components, and being removable, thus providing controlled drug delivery with minimal side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If frequent intravitreal injections are used to deliver drugs, then drug bioavailability is maintained, but side effects such as cataracts and retinal detachments increase
Solution Approach 1:
The hydrogel is injected in a flowable precursor state before crosslinking occurs, allowing the material to be delivered through a small gauge needle with minimal intrusion. The crosslinking then occurs in situ to form the final gel structure, preventing the need for repeated injections while maintaining drug availability
Solution Approach 2:
The hydrogel acts as an intermediary carrier that encapsulates the therapeutic agent and releases it over time. This mediator system provides sustained drug delivery without requiring frequent direct injections into the vitreous, thereby reducing side effects while maintaining bioavailability
2Reliability
If a formed hydrogel material is injected, then drug delivery is effective, but the injection requires a large gauge needle causing more trauma
Solution Approach 1:
The hydrogel material dynamically changes its physical state from a flowable precursor to a crosslinked gel after injection. This dynamic transformation allows the material to be injected through a small gauge needle in its fluid precursor state, then solidifies in situ to provide effective drug delivery without requiring a large needle
Solution Approach 2:
The viscosity and crosslinking state of the hydrogel are changed by adjusting parameters such as pH, temperature, or ionic strength after injection. This allows the material to be delivered in a low-viscosity flowable state through a small needle, then transformed into a higher-viscosity gel state for effective drug retention and delivery
3Stability of the object's composition
If the hydrogel adheres strongly to tissue, then drug release stability is enhanced, but removal or retrieval becomes difficult
Solution Approach 1:
The adhesive properties of the hydrogel are made tunable by changing parameters such as crosslinking density, hydrophilicity, or functional group composition. This allows the hydrogel to adhere sufficiently to tissue for stable drug release while maintaining enough flexibility and biocompatibility to allow for removal or degradation if needed
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
The hydrogel system enhances drug bioavailability, reduces side effects, and allows for prolonged drug release, minimizing the frequency of injections and inflammation, while being easily removable and conforming to the eye's shape without causing vision distortion.
Implementation Method 1
aqueous polymeric precursors are combined ex vivo in flowable concentrations/viscosities with a drug and injected intravitreally or via subconjunctival routes through a small gauge needle into the eye, where the precursors form a crosslinked hydrogel that releases the drug over time
Implementation Method 2
The hydrogel may be formulated to adhere to a tissue in or around the eye to enhance drug release effects and stability, to degrade to biocompatible components without causing inflammation
Data Source
AI summary
Some aspects of this disclosure relate to a method of treating an ophthalmic disease affecting an eye of a patient comprising forming a covalently-crosslinked hydrogel for controlled release of a therapeutic agent.