Nested Enteric Capsules for Targeted GI Cell Delivery

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Solution Overview

Problem

Current methods for delivering therapeutic mammalian cells orally face challenges in targeting specific sites within the gastrointestinal tract and maintaining cell viability and immune modulating activity during transit and release.

Innovation Solution

An oral delivery system comprising capsules with enteric coatings that release live mammalian cells at specific pH levels, allowing for targeted delivery to the ileum and colon, and utilizing a matrix with methyl cellulose and alginate gel to preserve cell viability and immune function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If oral delivery of therapeutic mammalian cells is attempted, then the cells can be administered non-invasively, but the cells lose viability and immune modulating activity during transit through the gastrointestinal tract

Engineering Contradiction:

ImproveEase of administrationVSAvoidCell viability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent employs a capsule-in-capsule nested structure where an inner capsule containing therapeutic cells is placed within an outer capsule. The inner capsule has an enteric coating that dissolves at specific pH levels (e.g., pH 6.2-6.5 for proximal colon targeting), while the outer capsule provides additional protection and may have different dissolution characteristics. This nested design allows sequential release of cells at different GI tract locations, maintaining cell viability during transit through the harsh gastric and intestinal environments.

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent introduces enteric coatings as intermediary protective layers between the therapeutic cells and the harsh GI tract environment. These coatings (e.g., Eudragit L100, cellulose acetate phthalate) act as mediators that protect cells from acidic pH, enzymatic degradation, and mechanical stress during oral transit, while allowing controlled release at target sites through pH-dependent dissolution.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of manufacture

If uniform enteric coating is used for oral delivery, then manufacturing is simplified, but site-specific delivery to different regions of the GI tract cannot be achieved

Engineering Contradiction:

ImproveManufacturing simplicityVSAvoidSite-specific delivery capability

Core Design Contradiction:

Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent divides the delivery system into segmented capsules with different enteric coating properties. The inner capsule may have an enteric coating designed to dissolve at pH 6.2-6.5 (targeting proximal colon), while the outer capsule has a coating that dissolves at higher pH 7.0-8.0 (targeting distal colon). This segmentation allows each capsule to be manufactured using standard enteric coating techniques, while the combination achieves site-specific delivery to different GI regions.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies different enteric coating formulations to different capsules or different portions of the delivery system. For example, the inner capsule receives an enteric coating with specific pH sensitivity (e.g., Eudragit L100 dissolving at pH 6.0-6.8), while the outer capsule receives a coating with different pH sensitivity (e.g., dissolving at pH 7.0-8.0). This local differentiation of coating properties enables targeted delivery to specific GI tract regions while maintaining manufacturability through standardized coating processes.

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If multiple capsules are used for targeted delivery to different GI regions, then site-specific delivery is improved, but device complexity increases

Engineering Contradiction:

ImproveSite-specific deliveryVSAvoidCapsule structure complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent simplifies the multi-capsule system by nesting the inner capsule within the outer capsule, creating a compact unified structure. The inner capsule (e.g., containing cells for proximal colon delivery) is placed inside the outer capsule (e.g., containing cells for distal colon delivery). This nested configuration reduces the physical complexity of handling multiple separate capsules while maintaining the ability to deliver cells to different GI regions through sequential pH-dependent dissolution of the nested capsules.

Inventive Principle:

Principle #7Nested doll (Nesting)

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 system effectively delivers live cells to targeted sites in the GI tract, maintaining high viability and immune modulating activity, as demonstrated by improved symptoms in a Crohn's-like disease mouse model and sustained cell viability for therapeutic benefits.

Implementation Method 1

the first enteric coating releases the first plurality of live mammalian cells at a pH of about 6.2 to about 6.5; and a second capsule, the second capsule comprising a second plurality of live mammalian cells, and a second enteric coating wherein the second enteric coating releases the second plurality of live mammalian cells at a pH of about 7 to 8

Methodology Applied

Scientific EffectpH-dependent dissolution: Phase Change