pH-Dependent Capsule for Targeted Oligonucleotide Delivery
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Solution Overview
Problem
Current treatments for ulcerative colitis, such as glucocorticosteroids and TNF-α inhibitors, have significant side effects and are not effective for all patients, leading to a need for alternative administration methods and formulations that can effectively target inflammatory bowel diseases like ulcerative colitis and Crohn's disease.
Innovation Solution
A formulation comprising an oligonucleotide with a CpG dinucleotide, specifically cobitolimod, combined with propylene glycol caprylate esters, encapsulated in a gelatin capsule with a pH-dependent coating to ensure targeted release in the gastrointestinal tract, allowing for oral administration and maximizing exposure at the site of inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If oligonucleotides are administered orally, then patient compliance and ease of administration are improved, but the oligonucleotides may be degraded in the gastrointestinal tract before reaching the target site
Solution Approach 1:
The oligonucleotide is pre-encapsulated in a protective capsule shell with pH-dependent release properties before administration. This preliminary encapsulation action protects the oligonucleotide from degradation in the acidic stomach environment and ensures it reaches the target site in the intestine intact, where it is then released at the appropriate pH level.
2Reliability
If conventional treatments like glucocorticosteroids and TNF-α inhibitors are used, then anti-inflammatory effects are achieved, but significant side effects occur
Solution Approach 1:
The formulation delivers the oligonucleotide specifically to the site of inflammation in the intestine through pH-dependent release from the capsule. This localized delivery ensures the active ingredient acts directly where needed (in the inflamed intestinal tissue) while minimizing systemic exposure and associated side effects throughout the rest of the body.
3Productivity
If the oligonucleotide is released too early in the gastrointestinal tract, then absorption is improved, but the oligonucleotide is exposed to degradation and does not reach the target site effectively
Solution Approach 1:
The capsule coating is designed to change its release properties based on pH parameters along the gastrointestinal tract. The coating remains intact in the acidic environment of the stomach (low pH) but dissolves and releases the oligonucleotide in the more neutral pH environment of the intestine, ensuring targeted delivery at the correct physiological parameter threshold.
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 formulation effectively induces clinical response and remission in patients with ulcerative colitis by ensuring the oligonucleotide is released at the appropriate pH in the gastrointestinal tract, thereby improving treatment efficacy and patient compliance.
Implementation Method 1
encapsulated in a gelatin capsule with a pH-dependent coating to ensure targeted release in the gastrointestinal tract
Data Source
AI summary
The present invention relates a formulation and capsule suitable for oral administration. The invention further relates to the use of the formulation and capsule for treating inflammatory bowel diseases, for instance ulcerative colitis (UC) or Crohn's disease.