Ceramide Lipid Conjugates for Mucosal Drug Delivery

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Solution Overview

Problem

Current drug delivery methods face challenges in transporting therapeutic agents across mucosal barriers and extending the half-life of drugs, as most protein therapeutics cannot be absorbed orally and are restricted to parenteral forms, limiting their effectiveness and requiring systemic administration which can cause toxicities.

Innovation Solution

The development of glycosphingolipid-therapeutic agent complexes, where therapeutic agents are attached to ceramides with specific fatty acid structures, allowing for targeted delivery across mucosal surfaces and enhanced intracellular trafficking to prolong drug half-life, using ceramides with short or long chain fatty acids and cis double bonds to direct trafficking pathways.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If therapeutic agents are administered parenterally to ensure drug availability, then drug half-life is extended, but systemic toxicities increase and mucosal delivery is not achieved

Engineering Contradiction:

Improvedrug half-lifeVSAvoidsystemic toxicities

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by modifying the therapeutic agent with specific lipid moieties (ceramides, glycosphingolipids, or sphingomyelins) that confer site-specific targeting properties. These lipid modifications enable the agent to preferentially accumulate at mucosal surfaces while reducing systemic distribution, thereby extending local half-life and minimizing systemic toxicities simultaneously

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent uses lipid molecules as intermediaries that mediate between the therapeutic agent and mucosal tissues. These lipid moieties act as carriers that facilitate mucosal penetration and retention, enabling the agent to achieve prolonged local exposure without requiring systemic administration

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of operation

If therapeutic agents are administered orally for mucosal delivery, then mucosal access is achieved, but drug absorption and bioavailability are limited

Engineering Contradiction:

Improvemucosal accessVSAvoiddrug absorption

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying the physicochemical properties of therapeutic agents through conjugation with lipid moieties. These modifications alter membrane permeability, stability, and interaction properties, enabling oral agents to successfully traverse mucosal barriers and achieve reliable absorption that would otherwise be impossible

Inventive Principle:

Principle #35Parameter changes

3Reliability

If therapeutic agents are introduced into cells for intracellular delivery, then cellular effectiveness is improved, but delivery complexity increases

Engineering Contradiction:

Improvecellular effectivenessVSAvoiddelivery complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies self-service by designing lipid-modified therapeutic agents that autonomously interact with cellular membranes and intracellular trafficking mechanisms. The lipid moieties enable the agents to self-direct into appropriate cellular compartments through natural membrane fusion and endocytic pathways, eliminating the need for complex external delivery systems

Inventive Principle:

Principle #25Self-service

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 effective delivery of therapeutic agents across mucosal barriers, prolongs drug half-life, and allows for topical administration, reducing systemic toxicities and enhancing treatment of mucosal diseases like inflammatory bowel disease.

Implementation Method 1

the fatty acid structure of ceramides has been shown to direct their trafficking and the subject compositions and methods can be used to harness intracellular trafficking in order to prolong the half-life of agents of interest

Methodology Applied

Scientific EffectIntracellular trafficking:

Implementation Method 2

allowing for the absorption (passage) of agents of interest, such as therapeutic agents, across epithelial and mucosal barriers

Methodology Applied

Scientific EffectMucosal absorption: Absorption (physical)

Data Source

PatentUS10806793B2Mucosal delivery of therapeutic molecules, proteins, or particles coupled to ceramide lipids

Publication Date: 2020.10.20 CHILDRENS MEDICAL CENT CORP

AI summary

Described herein are compositions and methods useful for allowing for the absorption (passage) of agents of interest, such as therapeutic agents, across epithelial and mucosal barriers and/or into certain subcellular compartments of the cell, such as the recycling endosome (RE), Golgi, and the endoplasmic reticulum (ER).