Temperature-Sensitive Gel for Sustained Protein Delivery
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Solution Overview
Problem
Current treatments for dry eye syndrome, cornea and conjunctiva damage, and skin trauma face challenges due to the short half-life of therapeutic proteins like EGF, leading to frequent administration needs and low efficacy from external applications like eye drops and sprays, which result in drug wastage and difficulty in evaluating treatment effectiveness.
Innovation Solution
A temperature-sensitive gel formulation containing recombinant human serum albumin/epidermal growth factor fusion protein, combined with glycine, poloxamer 188, and poloxamer 407, which forms a gel at body temperature, allowing for sustained release and prolonged action at the application site, enhancing treatment efficacy and reducing wastage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If external administration (eye drops, sprays) is used for cornea and conjunctiva damage, then the treatment can be applied locally, but the drug is quickly washed away and most of the drug flows to non-application sites by gravity, resulting in low absorption and drug wastage
Solution Approach 1:
The formulation utilizes temperature-sensitive gelation, transitioning from a liquid state during storage and administration to a gel state at body temperature (35-40°C). This phase transition enables the drug to remain at the application site through gravity-dependent gel formation, preventing wash-away and improving local retention without requiring complex delivery devices
Solution Approach 2:
The formulation changes its physical state parameter (viscosity) in response to temperature changes. At storage temperature (2-35°C), it remains liquid for easy administration; at application temperature (>35°C), it gels to enhance retention. This parameter change resolves the contradiction between ease of administration and drug retention
2Ease of operation
If traditional aqueous formulations (eye drops, sprays) are used, then the drug can be easily administered, but only a very small part of the drug is absorbed by local application while most flows to non-application sites
Solution Approach 1:
The temperature-sensitive gel formulation transitions from liquid to gel state at body temperature, creating a physical barrier that prevents drug wash-away and ensures reliable local absorption. The gel matrix traps the therapeutic protein, maintaining it at the application site and improving absorption reliability without complicating administration
3Duration of action of moving object
If recombinant human serum albumin/epidermal growth factor fusion protein is used, then the half-life is extended compared to monomeric EGF, but the half-life is still limited requiring frequent administration
Solution Approach 1:
The formulation performs preliminary action by forming a gel matrix before drug release, creating a sustained-release reservoir that slowly releases the fusion protein over time. This preliminary gel formation extends the effective half-life and reduces the need for frequent administrations
Solution Approach 2:
The temperature-sensitive gel provides continuous release of the fusion protein over an extended period. The gel matrix maintains the protein in a sustained-release state, ensuring continuous therapeutic action and reducing administration frequency compared to conventional formulations
4Duration of action of stationary object
If the formulation forms a gel at body temperature, then the drug remains at the application site for longer period and slow release is achieved, but the formulation must be liquid at storage temperature for easy preparation and administration
Solution Approach 1:
The formulation exploits reversible phase transition between liquid and gel states based on temperature changes. At storage temperature (2-35°C), it remains liquid for easy preparation and administration; at application temperature (>35°C), it gels to extend drug retention. This phase transition behavior resolves the contradiction between manufacturing ease and retention duration
Solution Approach 2:
The formulation's physical state parameter (viscosity) changes with temperature. The temperature-sensitive gelation mechanism allows the formulation to be liquid during manufacture and administration, then gel at body temperature to provide sustained release, eliminating the need for separate formulation designs for different stages
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 formulation maintains biological activity, prolongs the half-life of the fusion protein, improves treatment effectiveness for dry eye syndrome, cornea and conjunctiva damage, and skin trauma, while being safe and non-irritating, with increased drug utilization and faster repair times.
Implementation Method 1
the formulation is capable of maintaining a clear and transparent aqueous dosage form under the condition of 0-35° C., and be gel-like at 35° C. or above
Implementation Method 2
temperature sensitive gel damage repair formulation... forms a gel at body temperature, allowing for sustained release
Data Source
AI summary
The present invention belongs to the technical field of biomedical formulations. Provided are a temperature sensitive gel damage repair formulation and an application thereof. The formulation includes 0.01-5 mg/mL rHSA/EGF, 1.9-2.6% m/m glycine, 3.9-6.2% m/m poloxamer 188, 16.3-18.2% m/m poloxamer 407, and 0.5-100 mM phosphate buffer.