Cross-linked Maltodextrin Oral Insulin Delivery
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Solution Overview
Problem
The oral administration of biopharmaceuticals like insulin is hindered by the gastro-intestinal tract's barrier, leading to inefficient uptake and rapid degradation, resulting in unsatisfactory pharmacokinetic behavior and increased risk of hypoglycemia due to high insulin peaks and quick decreases, necessitating repeated administrations.
Innovation Solution
A cross-linked maltodextrin delivery system is developed, which provides a safer and more efficient oral delivery of biological actives by slowing insulin release and maintaining bioavailability, using a cross-linked maltodextrin with pyromellitic dianhydride as a cross-linking compound, allowing for prolonged insulin activity and reduced risk of hypoglycemia.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cross-linked cyclodextrin is used as a delivery system for oral insulin, then insulin can remain intact and cross the membrane, but it causes high peak blood insulin leading to harmful hypoglycemia
Solution Approach 1:
The patent changes the chemical structure parameter by replacing cyclodextrin with maltodextrin as the base material, and modifies the cross-linking parameters by using different cross-linking agents (epichlorohydrin, glutaraldehyde, or genipin) to create a delivery system that releases insulin more gradually, reducing the peak blood insulin level while maintaining therapeutic efficacy
Solution Approach 2:
The invention creates a composite material system combining maltodextrin with specific cross-linking agents to form a cross-linked maltodextrin matrix that provides controlled release properties, combining the benefits of structural integrity with controlled insulin release kinetics to avoid hypoglycemia
2Ease of operation
If cross-linked cyclodextrin delivery system is used, then insulin can be delivered orally, but blood insulin decreases quickly requiring repeated administrations
Solution Approach 1:
The patent modifies the release kinetics parameters by changing the cross-linking degree and type, using different cross-linking agents that provide varying levels of mesh density in the delivery matrix, thereby extending the duration of insulin release and activity in the bloodstream to reduce the frequency of administrations
Solution Approach 2:
The invention creates a dynamic release system where the cross-linked maltodextrin matrix progressively releases insulin over time, adapting the release rate to maintain therapeutic levels throughout the day, thereby extending the effective duration of action compared to conventional delivery systems
3Ease of operation
If biopharmaceuticals are administered orally, then patient comfort and compliance improve, but the gastro-intestinal tract degrades the biopharmaceuticals and prevents efficient uptake
Solution Approach 1:
The patent applies preliminary protective action by encapsulating insulin within the cross-linked maltodextrin matrix before oral administration, which protects the biopharmaceutical from degradation in the harsh gastro-intestinal environment and facilitates its subsequent absorption, thereby maintaining reliability while enabling comfortable oral administration
Solution Approach 2:
The cross-linked maltodextrin acts as an intermediary carrier that shields the insulin from harmful gastro-intestinal conditions (acidity, enzymes) during transit, and simultaneously facilitates membrane crossing and absorption, thus resolving the contradiction between oral administration benefits and gastrointestinal degradation risks
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 cross-linked maltodextrin system achieves a longer-lasting insulin release, reducing the risk of hypoglycemia by minimizing peak blood insulin levels and maintaining effective insulin levels for a longer period, thus improving pharmacokinetic properties and bioavailability.
Implementation Method 1
the large molecular size and/or hydrophilic nature of biopharmaceuticals like proteins prevent them from diffusing across the mucin barrier
Implementation Method 2
The delivery system of the invention is able to markedly increase the pharmacokinetic profile of active proteins after oral administration... provokes slower release of insulin
Implementation Method 3
uses a cross-linked maltodextrin... using a cross-linked maltodextrin with pyromellitic dianhydride as a cross-linking compound
Implementation Method 4
Before reaching the systemic circulation, biopharmaceuticals have to retain their intact structure, integrity and conformation through the stomach and intestine. However biopharmaceuticals are particularly sensitive to the gastro-intestinal tract environment, mainly due to the high gastric acidity, and to the presence of hydrolyzing enzymes
Implementation Method 5
insulin loaded in such cross-linked material, was not only capable of remaining intact into the gastrointestinal tract, but was also capable of crossing its membrane and to enter the plasmatic compartment
Data Source
AI summary
The invention relates to oral administration of biological actives, in particular of insulin, comprising the use of a cross-linked starchy material as a delivery system.