Microsphere Formulation for Targeted Drug Delivery
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Solution Overview
Problem
Current pharmaceutical delivery methods often result in systemic administration, leading to unintended side effects and reduced efficacy due to the inability to target specific tissues or organs effectively, particularly for growth factors and cancer chemotherapeutic agents.
Innovation Solution
A pharmaceutical formulation comprising spherical particles with a mean diameter of 15 microns, primarily containing a biodegradable excipient and an active ingredient, designed for intra-arterial administration upstream of the target tissue, which traps in capillaries, restricting systemic circulation and allowing localized action.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If systemic administration is used, then the active ingredient can reach the target tissue, but the active ingredient also distributes to non-target tissues causing side effects
Solution Approach 1:
The pharmaceutical formulation segments the active ingredient delivery by using particles of specific size (10-20 microns) that can be administered systemically but will selectively accumulate in target tissues through the enhanced permeability and retention effect, thereby separating target tissue exposure from non-target tissue exposure
Solution Approach 2:
The formulation achieves local quality by creating particles with specific physical characteristics (size, surface properties) that enable selective accumulation in target tissues with different vascular permeability, allowing the same formulation to have different local effects in different tissues
2Reliability
If higher doses are administered to ensure target tissue coverage, then target tissue efficacy is improved, but systemic toxicity increases
Solution Approach 1:
The formulation segments the dose distribution by using particles that remain in circulation longer and accumulate selectively in target tissues, allowing a lower total dose to achieve the same target tissue concentration that would require a higher dose with small molecules that distribute systemically
Solution Approach 2:
The particle formulation acts as an intermediary carrier that protects the active ingredient from systemic distribution while facilitating selective accumulation in target tissues through passive targeting mechanisms related to vascular permeability differences
3Ease of manufacture
If the active ingredient is delivered upstream of the target tissue, then targeted delivery is achieved, but particle size must be controlled to prevent embolism
Solution Approach 1:
The formulation changes the physical parameter of particle size to a specific range (10-20 microns) that balances two opposing requirements: being large enough to be retained in target tissue capillaries for localized action, yet small enough to avoid causing embolism in larger vessels during upstream administration
Solution Approach 2:
The formulation applies local quality by creating a narrow particle size distribution that provides different local effects: particles of 10-20 microns are retained in target tissue capillaries (5-10 microns) for localized therapy, while the uniform size prevents embolism in larger vessels during upstream delivery
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 approach enables targeted delivery with reduced side effects and increased therapeutic window by maintaining the active ingredient in the target tissue for a therapeutically effective period, allowing lower doses and minimizing systemic exposure.
Implementation Method 1
the diameter of 15±1 microns confers upon the particles retention in a target tissue following administration of the pharmaceutical formulation upstream of the target tissue
Data Source
Figure 1A~1E
Figure 2A~2I
Figure 3A~3I
AI summary
The present invention relates to pharmaceutical formulations suitable for targeting particular tissue and/or organ(s) with a formulated active ingredient, for example when administered upstream of the target organ or tissue, and to use of the same in treatment, methods of treatment administering the same and methods of preparing the formulations. The pharmaceutical formulations of the invention are for parenteral administration to a target tissue and comprise particles containing an active ingredient, and a biodegradable excipient, wherein 90% or more of the particles have a diameter of between 10 and 20 microns and the formulation is substantially free of particles with a diameter greater than 50 microns and less than 5 microns, such that where the formulation is administered upstream of the target tissue the ability of the active to pass through the target tissue and pass into systemic circulation is restricted.