Liposome Formulation for Rapamycin Delivery

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Solution Overview

Problem

Rapamycin, a key inhibitor of the mammalian target of rapamycin (mTOR), has low aqueous solubility and bioavailability, limiting its clinical applications as an anti-cancer agent due to low bioavailability and high toxicity associated with its formulations, particularly in oral and injectable forms.

Innovation Solution

Development of a liposome formulation encapsulating rapamycin or its analogs with specific lipid ingredients such as cholesterol, phosphatidylcholine, and PEG-modified lipids, which provides stability before and after lyophilization, enhances bioavailability, and reduces toxicity, allowing for effective tumor inhibition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If rapamycin is administered in traditional formulations, then the drug can be delivered to patients, but the bioavailability is low (14-18%) and toxicity is high

Engineering Contradiction:

ImprovebioavailabilityVSAvoidtoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses liposomes as intermediary carriers to deliver rapamycin. The liposome structure with specific lipid composition (cholesterol, phosphatidylcholine, PEG-modified lipids) acts as a mediator between the drug and biological system, improving bioavailability to over 80% while reducing toxicity by controlling drug release and protecting tissues from direct drug exposure.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical and chemical parameters of rapamycin by encapsulating it in liposomes. This transforms the drug from a poorly soluble small molecule to a stable liposomal formulation with enhanced solubility, improved pharmacokinetics, and reduced side effects, achieving bioavailability exceeding 80% compared to traditional formulations.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If rapamycin solubility is improved through chemical modification to create rapalogs, then bioavailability may improve, but the drugs remain highly allergenic due to excipients in injectable forms

Engineering Contradiction:

ImprovebioavailabilityVSAvoidallergenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs a flexible liposomal shell composed of biocompatible lipids including PEG-modified phospholipids. This flexible membrane structure encapsulates rapamycin or its analogs, providing a safe delivery vehicle that reduces allergenicity compared to traditional excipients while maintaining high bioavailability through controlled drug release.

Inventive Principle:

Principle #30Flexible shells and thin films

Solution Approach 2:

The patent creates a composite liposomal formulation combining multiple lipid components (cholesterol, phosphatidylcholine, PEG-lipids) with rapamycin or its analogs. This composite material approach produces a stable, biocompatible formulation that achieves high bioavailability while minimizing allergic reactions, overcoming the limitations of both traditional formulations and rapalog excipients.

Inventive Principle:

Principle #40Composite materials

3Reliability

If liposome formulation is developed to improve bioavailability, then drug delivery efficiency increases, but the formulation complexity increases

Engineering Contradiction:

ImprovebioavailabilityVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the complex liposome formulation into defined lipid components with specific ratios (cholesterol, phosphatidylcholine, PEG-modified lipids). This segmentation approach allows systematic optimization of each component's contribution to stability and bioavailability while maintaining manageable formulation complexity through standardized preparation methods.

Inventive Principle:

Principle #1Segmentation

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 liposome formulation achieves high bioavailability, superior tumor inhibition, and reduced toxicity, offering a more effective and safer delivery method for rapamycin and its derivatives compared to traditional formulations.

Implementation Method 1

a liposome comprising a lipid ingredient encapsulating rapamycin or an analog thereof

Methodology Applied

Scientific EffectEncapsulation: Absorption (physical)

Implementation Method 2

The lipid ingredient is selected from the group consisting of: cholesterol, phosphatidylcholine (PC), L-α-phosphatidylcholine (EggPC), 1,2-Didecanoyl-sn-glycerol-3-phosphocholine (DDPC), 1,2-distearoyl-sn-glycerol-3-phosphorylethanolamine (DSPE), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylethanolamine (DOPE), dipalmitoyl phosphatidylcholine (DPPC), hydrogenated soy phosphatidylcholine (HSPC)

Methodology Applied

Scientific EffectLiposome formation: Amphiphiles

Data Source

PatentEP4268800A1Liposome comprising rapamycin or a derivative thereof and use thereof in therapy

Publication Date: 2023.11.01 PRESCIENCE BIOTECHNOLOGY INC

Figure 1(A)~1(B)
Figure 2(A)~2(B)
Figure 3(A)~3(B)

AI summary

The present disclosure relates to a lipid-based formulation comprising rapamycin and derivatives thereof, and also relates to using the formulation for treatment of diseases or conditions, such as cancers, immuo-related disease, etc.