Thermosensitive Liposomes Gel to Liquid Phase Transition

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Solution Overview

Problem

There is a need for liposomes that can encapsulate therapeutic agents and undergo a gel to liquid phase transition at temperatures achievable in a subject, specifically for targeted drug delivery in thermosensitive applications.

Innovation Solution

Thermosensitive liposomes composed of phosphatidylcholine, phosphatidylglycerol, lysolipid, and PEGylated phospholipids, with a gel to liquid phase transition temperature range of 39.0°C to 45°C, allowing for controlled release of active agents such as anticancer drugs when heated to specific body temperatures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If conventional liposomes are used to encapsulate therapeutic agents, then drug delivery capability is achieved, but the gel to liquid phase transition temperature is not within the range obtainable in the subject

Engineering Contradiction:
Improvegel to liquid phase transition temperatureVSAvoidtargeted drug delivery reliability
Core Design Contradiction:
TemperatureVSReliability

Solution Approach 1:

The patent modifies the phase transition temperature of liposomes by changing the lipid composition parameters. Specifically, it uses a combination of phosphatidylcholine (DPPC), phosphatidylglycerol (DSPG), and lysolipid (MSPC) in specific ratios to achieve a phase transition temperature between 39.0°C and 45°C, which is within the obtainable temperature range in human subjects through mild heating.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite liposome structure using multiple lipid components with different properties. The combination of DPPC (which has a high phase transition temperature), DSPG (which lowers the phase transition temperature), and MSPC (which modifies membrane fluidity) produces a composite material with the desired phase transition temperature range for targeted drug delivery.

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If thermosensitive liposomes with phase transition temperature in subject-obtainable range are formulated, then targeted drug delivery to heated areas is achieved, but specific lipid composition ratios must be precisely controlled

Engineering Contradiction:
Improvecontrolled drug release at target siteVSAvoidlipid composition ratio control
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent establishes specific parameter ranges for lipid composition to achieve the desired phase transition temperature. By defining the weight ratios of DPPC (60-80%), DSPG (6-12%), and MSPC (6-12%), the patent creates a formulation window that ensures reliable targeted drug delivery while accounting for manufacturing variability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent assigns different functional roles to specific lipid components within the liposome structure. DPPC provides the base membrane structure and high phase transition temperature, DSPG lowers the phase transition temperature to the desired range, and MSPC modifies membrane fluidity and stability. This functional differentiation allows each component to contribute optimally to the overall performance.

Inventive Principle:
Principle #3Local quality

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 thermosensitive liposomes effectively deliver therapeutic agents to targeted sites by transitioning from a gel to liquid state at body temperatures, enhancing drug delivery and treatment efficacy, particularly in cancer therapy by releasing active agents like docetaxel and carboplatin in close proximity to diseased tissues.

Implementation Method 1

When the thermosensitive liposome reaches the heated area, it undergoes a gel to liquid phase transition and releases the active agent

Methodology Applied
Scientific EffectGel to liquid phase transition: Phase Change

Data Source

PatentEP2217209B1Novel thermosensitive liposomes containing therapeutic agents
Publication Date: 2018.06.06 CELSION CORP
  • EP2217209B1 patent drawingFigure 1
  • EP2217209B1 patent drawingFigure 2
  • EP2217209B1 patent drawingFigure 3

AI summary

A thermosensitive liposome for the delivery of active agents and a composition thereof are disclosed, wherein the liposome comprises at least one phosphatidylcholine, at least one phosphatidylglycerol and at least one lysolipid, and the gel to liquid phase transition temperature of said liposome is from 39 0°C to 45°C.