Thermoreversible Gel for Inner Ear Drug Delivery
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Solution Overview
Problem
Current treatments for inner ear diseases face challenges such as limited delivery of active agents due to the blood-labyrinth barrier, osmotic imbalances, infections, and structural damage, leading to hearing loss and other complications.
Innovation Solution
A sterile, controlled release intratympanic composition comprising a neurotrophic growth factor as an aural pressure modulating agent, combined with a polyoxyethylene-polyoxypropylene triblock copolymer (Poloxamer 407) in a thermoreversible gel form, designed to provide sustained release for at least 3 days and maintain the ionic balance of inner ear fluids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If active agents are administered to treat inner ear diseases, then treatment efficacy is improved, but delivery is limited due to the blood-labyrinth barrier
Solution Approach 1:
The patent uses the round window membrane as an intermediary pathway to bypass the blood-labyrinth barrier. By administering compositions through the round window, active agents can reach the inner ear without crossing the restrictive BLB, thereby improving delivery quantity while maintaining treatment efficacy
Solution Approach 2:
The patent employs controlled release formulations that modify the release parameters of active agents over time. This sustained release mechanism ensures adequate drug concentration reaches the inner ear despite the barrier, resolving the contradiction between delivery quantity and treatment efficacy
2Duration of action of moving object
If sustained release composition is used, then duration of action is improved, but complexity of formulation is increased
Solution Approach 1:
The patent utilizes phase transition properties of poloxamer 407, which transitions from liquid at lower temperatures to gel at body temperature. This natural phase change enables sustained release functionality without complex mechanical structures, achieving extended duration of action while keeping the formulation relatively simple
Solution Approach 2:
The patent combines poloxamer 407 with neurotrophic growth factors to create a composite formulation. The poloxamer provides the sustained release matrix while the growth factor provides the therapeutic action, achieving extended duration through material composition rather than complex device design
3Quantity of substance
If intratympanic composition is administered, then direct delivery to inner ear is improved, but risk of osmotic imbalance and infection is increased
Solution Approach 1:
The patent carefully controls the osmolarity parameter of the composition to match physiological conditions, preventing osmotic imbalance. The formulation is designed with specific osmolarity ranges that are isotonic to inner ear fluids, allowing direct delivery while eliminating the harmful effect of osmotic disruption
Solution Approach 2:
The patent employs sterile techniques and preservatives to create a microenvironment that prevents microbial contamination. By maintaining an inert, sterile formulation environment, the composition can be administered directly to the inner ear through the round window without introducing infection risk
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 composition effectively delivers the active agent to the inner ear, reducing the risk of osmotic imbalances and infections, while providing prolonged exposure to the neurotrophic growth factor, thereby improving treatment efficacy and patient compliance.
Implementation Method 1
the composition is an auris-acceptable thermoreversible gel
Implementation Method 2
the composition provides sustained release of the aural pressure modulating agent into the inner ear for a period of at least 3 days
Implementation Method 3
sterile water, q.s., buffered to provide a perilymph-suitable pH between about 6.0 and about 7.6
Implementation Method 4
between about 0.1 mg/mL to about 70 mg/mL of an aural pressure modulating agent, wherein the aural pressure modulating agent is a neurotrophic growth factor
Data Source
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AI summary
Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.