Biodegradable Microparticles for Sustained Ocular Drug Delivery
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Solution Overview
Problem
Current ophthalmic drug delivery methods, such as intravitreous injections, pose risks and discomfort, and existing sustained release formulations are not effective for large, water-soluble compounds or biotherapeutics, necessitating the development of safer and more efficient delivery systems for therapeutic agents like anti-VEGF agents.
Innovation Solution
The development of syringable microparticles made from biodegradable polymers like PLGA, which can encapsulate biologically active agents like pegaptanib, providing sustained release over several months with minimal initial burst, suitable for ophthalmic administration through a 27-gauge needle or smaller, ensuring effective and prolonged therapeutic levels in the eye.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intravitreous injection is administered frequently to maintain therapeutic levels, then therapeutic efficacy is improved, but patient comfort and safety deteriorate due to repeated invasive procedures
Solution Approach 1:
The patent segments the therapeutic agent into microparticle formulations that can be administered as a single sustained-release injection. The microparticles are divided into size ranges (e.g., 1-100 μm, 10-50 μm) that enable them to be injected through fine needles while maintaining sustained release properties, thus reducing the need for frequent repeat injections and associated patient discomfort and risks.
Solution Approach 2:
The patent applies preliminary action by formulating the therapeutic agent into sustained-release microparticles before administration. This pre-formulation ensures that the drug is released gradually over time (e.g., 1-6 months), eliminating the need for frequent repeat injections and the associated discomfort and safety risks to patients.
2Object-affected harmful factors
If sustained release formulations are used to reduce injection frequency, then patient comfort and safety are improved, but existing formulations fail to deliver large water-soluble compounds and biotherapeutics effectively
Solution Approach 1:
The patent applies parameter changes by modifying the microparticle formulation parameters to achieve sustained release of water-soluble compounds and biotherapeutics. Specifically, the patent uses biodegradable polymers (e.g., PLGA, PLA, PGA) with controlled composition and molecular weight, adjusts the drug-to-polymer ratio, and controls microparticle size and surface properties to enable sustained release of large, water-soluble molecules while maintaining patient comfort and safety.
Solution Approach 2:
The patent uses composite materials by combining biodegradable polymers (e.g., PLGA, PLA, PGA) with water-soluble therapeutic agents. The composite microparticle structure allows the hydrophilic drug to be encapsulated within or on the polymer matrix, enabling sustained release through polymer degradation while maintaining compatibility with large, water-soluble compounds and biotherapeutics.
3Ease of operation
If microparticles are made small enough to be syringable through fine needles, then ease of administration is improved, but sustained release duration may be limited
Solution Approach 1:
The patent applies local quality by creating microparticles with specific size distributions (e.g., 1-100 μm, 10-50 μm) that are small enough to be syringable through 27-gauge needles while maintaining sufficient mass for sustained release. The patent also creates heterogeneous mixtures of different sized microparticles, where smaller particles provide immediate release and larger particles provide extended release, achieving both syringability and prolonged duration of action.
Solution Approach 2:
The patent applies another dimension by considering the three-dimensional size distribution of microparticles rather than a single size parameter. The patent formulates microparticles with specific size ranges and distributions that enable them to pass through fine needles while maintaining sufficient total volume and drug load for sustained release over extended periods (e.g., 1-6 months).
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 microparticles offer a safe, comfortable, and effective method for sustained delivery of therapeutic agents, reducing the frequency of injections and maintaining therapeutic levels for extended periods, thereby minimizing risks associated with frequent intravitreous injections.
Implementation Method 1
Several techniques for the production of lactide/glycolide polymer microparticles containing biological or chemical agents by an emulsion-based manufacturing technique have been reported. In general, the methods include preparation of a first phase consisting of an organic solvent, a polymer and a biological or chemical agent dissolved or dispersed in the first solvent. A second phase comprises water and a stabilizer and, optionally, the first solvent. The first and second phases are emulsified and, after an emulsion is formed, the first solvent is removed from the emulsion, producing hardened microparticles.
Implementation Method 2
Following administration, drug then is released via diffusion out of, or via erosion of the matrix.
Data Source
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AI summary
Formulations for controlled, sustained release of biologically active agents for the treatment of ocular disorders have been developed. These formulations are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof. The microparticles are characterized by low burst levels and efficient drug loading and sustained release.