Siosome Carrier Targeting System for Intracellular Drug Delivery

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Solution Overview

Problem

Current methods for delivering therapeutic agents, such as doxorubicin and siRNA, face challenges in achieving targeted intracellular delivery and release while minimizing toxicity and maintaining stability in circulation, due to rapid removal by the reticulo-endothelial system and difficulty in penetrating cellular compartments.

Innovation Solution

A carrier and targeting system comprising siosomes and siosome-liposomes with covalently attached cationic lipids and PEGylated organosilicon compounds, designed for stable circulation and triggered release within acidic lysosomal environments, allowing for specific targeting and reduced toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If liposomal encapsulation is used to deliver doxorubicin, then therapeutic action is increased and toxicity is reduced, but the lipids and liposomes themselves exhibit significant toxicity

Engineering Contradiction:
ImprovetoxicityVSAvoidtherapeutic efficacy
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent introduces siosomes as an intermediary carrier system that mediates between the therapeutic agent (doxorubicin) and the body's biological systems. The siosome composition includes organosilicon compounds, phospholipids, and cholesterol, creating a novel delivery vehicle that avoids the direct toxicity issues of conventional liposomes while maintaining therapeutic efficacy through controlled release and targeted delivery mechanisms

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If conventional liposomes are used for drug delivery, then active substance can be delivered to target sites, but rapid removal by reticulo-endothelial system occurs

Engineering Contradiction:
Improvedelivery efficiencyVSAvoidcirculation time
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent modifies the physical and chemical parameters of the carrier system by incorporating organosilicon compounds with specific molecular structures and charge characteristics. The siosome composition adjusts surface charge, size, and compositional ratios to optimize circulation time and resist clearance by the reticulo-endothelial system, thereby enhancing delivery efficiency to target sites

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If high lipid concentration is used in DXR/liposomes, then intracellular delivery is achieved, but stability in circulation is compromised

Engineering Contradiction:
Improveintracellular deliveryVSAvoidcirculation stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent creates a composite material system combining organosilicon compounds, phospholipids, and cholesterol in specific ratios. This composite siosome structure provides both the necessary intracellular delivery capability and circulation stability, with the organosilicon component contributing to enhanced structural integrity and resistance to degradation while maintaining the amphipathic properties needed for membrane interaction

Inventive Principle:
Principle #40Composite materials

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 system achieves enhanced intracellular delivery and release of therapeutic agents with improved stability and reduced toxicity, increasing the effective concentration of drugs like doxorubicin and siRNA, while minimizing adverse effects on healthy cells.

Implementation Method 1

The invention relates to a carrier and targeting system comprising a siosomal composition for the intracellular delivery and release of a siosome- and/or siosome-liposome-entrapped or encapsulated active substance

Methodology Applied
Scientific EffectEndocytosis:

Implementation Method 2

The invention relates to the use of cationic lipids, which are covalently linked to the silicone central atom of the silanes, sugar silanes and/or amino-sugar silanes

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 3

Such long circulating liposomes may include a surface coat of flexible water soluble chains that act to prevent interaction between the liposome and plasma components

Methodology Applied
Scientific EffectSteric hindrance:

Implementation Method 4

designed for stable circulation and triggered release within acidic lysosomal environments

Methodology Applied
Scientific EffectpH-triggered release:

Data Source

PatentEP2563337B1Carrier and targeting system comprising a siosomal composition for intracellular delivery and targeting of active substance
Publication Date: 2017.07.26 SALAMA ZOSER B
  • EP2563337B1 patent drawingFigure 1
  • EP2563337B1 patent drawingFigure 2
  • EP2563337B1 patent drawingFigure 2suiite

AI summary

The invention relates to a carrier and targeting system comprising a siosomal composition for the intracellular delivery and release of a siosome- and/or siosome-liposome-entrapped or encapsulated active substance or therapeutic agent. The invention further relates to the targeted release and delivery of doxorubicin, cis-platin, carbo-platin and/or oxali-platin using said carrier and targeting system. The invention relates to carrier and targeting systems that comprise of charged lipid species, such as cationic or anionic lipids. The invention also relates to a method for preparing such carrier and targeting systems and methods for their administration, particularly in the treatment of cancer.