Intestinal Wall Delivery of Factor VIII to Bypass GI Degradation
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Solution Overview
Problem
Current treatments for clotting disorders like hemophilia and von Willebrand's disease face challenges due to poor oral tolerability, degradation in the stomach, and the development of inhibitory antibodies from intravenous and subcutaneous drug delivery methods, necessitating improved oral delivery methods that avoid these issues.
Innovation Solution
A biodegradable solid tissue-penetrating member containing stabilized Factor VIII is orally delivered to penetrate the intestinal wall and release the clotting factor into the peritoneal cavity, where it degrades to achieve therapeutic plasma concentrations, minimizing antibody production and improving efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If clotting factor preparations are administered via conventional routes (subcutaneous injection, intravenous infusion), then the therapeutic effect is achieved, but the quality of life is reduced due to frequent administration and burden on patients
Solution Approach 1:
The patent replaces the mechanical injection/infusion system with an oral capsule delivery system. The clotting factor preparation is encapsulated in a swallowable capsule that releases the medication in the intestinal tract, eliminating the need for needles, pumps, and trained personnel while maintaining therapeutic effectiveness through targeted intestinal absorption.
Solution Approach 2:
The patent introduces an intermediary delivery system (the capsule and intestinal tract) between the clotting factor preparation and the bloodstream. The capsule protects the preparation during gastric passage and enables controlled release in the intestinal tract, serving as a mediator that facilitates oral administration while preserving the activity of the clotting factor.
2Ease of operation
If clotting factor preparations are delivered orally, then the quality of life is improved, but the preparation may be degraded by gastric acid and enzymes
Solution Approach 1:
The patent employs a capsule shell as a protective barrier that allows the clotting factor preparation to pass through the harsh gastric environment intact. The shell is designed to be resistant to gastric acid and enzymes, protecting the sensitive protein preparation until it reaches the more favorable intestinal tract for release and absorption.
Solution Approach 2:
The patent exploits the parameter change in pH and enzyme concentration between the stomach and intestinal tract. The capsule is designed to withstand gastric conditions (low pH, high enzyme activity) and release its contents in the intestinal tract (higher pH, lower enzyme activity), where the clotting factor preparation is more stable and can be effectively absorbed.
3Ease of operation
If the intestinal tract is used as the delivery site, then oral administration is enabled, but the preparation must survive passage through the stomach
Solution Approach 1:
The capsule shell serves as a protective flexible barrier that shields the clotting factor preparation from gastric acid and enzymes during passage through the stomach. The shell maintains the integrity of the preparation while allowing it to reach the intestinal tract, where the harmful gastric environment no longer applies.
Data Source
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AI summary
Embodiments provide devices, preparations and methods for delivering therapeutic agents (TAs) such as clotting factors (CFs), e.g., Factor VIII (FVIII) including PEGylated and other forms of stabilized FVIII, within the GI tract. Many embodiments provide a swallowable device e.g., a capsule for delivering TAs into the intestinal wall (IW). Embodiments also provide TA preparations configured to be contained within the capsule, advanced from the capsule into the IW and/or surrounding tissue (ST) and degrade to release the TA into the bloodstream to produce a therapeutic effect (e.g., improved clotting). The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the IW or ST (e.g., the peritoneal cavity). Embodiments are particularly useful for delivery of CFs for treatment of clotting disorders (e.g., hemophilia) where such CFs are poorly absorbed and/or degraded within the GI tract.