Sterically Stabilized Cationic Liposomes for CpG ODN Delivery

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Solution Overview

Problem

Phosphorothioate CpG oligodeoxynucleotides used in vivo are rapidly eliminated due to adsorption onto serum proteins and degradation by serum nucleases, limiting their therapeutic efficacy.

Innovation Solution

Encapsulation of CpG oligodeoxynucleotides within sterically stabilized cationic liposomes (SSCL) to enhance bioavailability and immune cell uptake, combined with targeted biological agents like chimeric molecules for synergistic tumor growth reduction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If phosphorothioate CpG oligodeoxynucleotides are administered in vivo, then immune stimulation activity is achieved, but rapid elimination occurs due to adsorption onto serum proteins and degradation by serum nucleases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidbioavailability

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent uses sterically stabilized cationic liposomes as an intermediary carrier to deliver CpG oligodeoxynucleotides. The liposomes protect the oligonucleotides from serum proteins and nucleases while facilitating cellular uptake, thereby extending bioavailability and maintaining therapeutic efficacy.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the physical and chemical parameters of the CpG oligodeoxynucleotides by incorporating them into liposomal structures. This changes their circulation characteristics, protecting them from degradation and adsorption, thus extending their duration of action in vivo.

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If CpG oligodeoxynucleotides are delivered without encapsulation, then direct immune cell interaction is possible, but rapid degradation and protein adsorption occur

Engineering Contradiction:

Improvedirect deliveryVSAvoidstability in circulation

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The sterically stabilized cationic liposomes serve as a mediator between the CpG oligodeoxynucleotides and the biological environment. They provide protection during circulation while enabling eventual delivery to immune cells, balancing stability and ease of delivery.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Duration of action of moving object

If liposome encapsulation is used to protect CpG oligodeoxynucleotides, then bioavailability is prolonged, but device complexity increases

Engineering Contradiction:

ImprovebioavailabilityVSAvoidencapsulation system

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent employs sterically stabilized cationic liposomes with specific compositional parameters (cationic lipids, cholesterol, PEG-lipids in defined ratios) that provide effective protection and prolonged circulation. This targeted parameter optimization achieves bioavailability extension without excessive complexity.

Inventive Principle:

Principle #35Parameter changes

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 SSCL encapsulation method significantly prolongs the bioavailability and therapeutic efficacy of CpG oligodeoxynucleotides, effectively stimulating an immune response and impairing solid tumor growth by synergistic action with targeted agents.

Implementation Method 1

sterically stabilized cationic liposomes (SSCL) encapsulating a K type oligodeoxynucleotide (ODN) including a CpG motif can be used to effectively deliver the ODN to a cell

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

phosphorothioate CpG ODN used in vivo are rapidly eliminated from the circulation due to adsorption onto serum proteins... sterically stabilized cationic liposomes (SSCL) encapsulating a K type oligodeoxynucleotide

Methodology Applied

Scientific EffectSteric stabilization:

Data Source

PatentUS7666674B2Use of sterically stabilized cationic liposomes to efficiently deliver CPG oligonucleotides in vivo

Publication Date: 2010.02.23 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Sterically stabilized cationic liposomes (SSCL) encapsulating a K type oligodeoxynucleotide (ODN) including a CpG motif are disclosed. These SSCL encapuslating a K type ODN can be used to effectively deliver the ODN to a cell. A novel method is also disclosed for producing the SSCL encapsulating the K type ODN. Administration of the SSCL encapsulating a K type ODN and a chemotherapeutic agent, such as a chimeric molecule comprising a targeting molecule selected from the group consisting of an IL-13, and an anti-IL-13 receptor antibody; and an effector molecule selected from the group consisting of a Pseudomonas exotoxin, a Diphtheria toxin, and a radionuclide, can be used to dramatically reduce the growth of solid tumors.