Lyophilized Nanoparticle Compositions for Immunogenic Suspensions

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Solution Overview

Problem

Existing particulate carrier technologies for immunological responses, such as microparticles, face challenges in ease of preparation, antigen loading capacity, and aseptic processing, particularly in forming effective nanoparticle suspensions for immunogenic compositions.

Innovation Solution

Development of sterile lyophilized nanoparticle compositions comprising biodegradable polymers, surfactants, cryoprotective agents, and antigens, which can form immunogenic nanoparticle suspensions with sizes less than 250 nm, allowing for high antigen loading and simplified preparation without the need for high-shear homogenization or strict aseptic conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If microparticle carriers are used to present antigens to the immune system, then immune response is enhanced, but particle size is too large for optimal lymph node trapping and retention

Engineering Contradiction:

Improveimmune response effectivenessVSAvoidparticle size

Core Design Contradiction:

ReliabilityVSVolume of moving object

Solution Approach 1:

The patent changes the size parameter from microparticle scale to nanoparticle scale (20-200 nm diameter), optimizing the particles for lymph node trapping and retention while maintaining immunogenicity. This parameter change resolves the contradiction by finding the optimal size range that balances immune response enhancement with effective lymph node targeting.

Inventive Principle:

Principle #35Parameter changes

2Volume of moving object

If high-shear homogenization is used to form nanoparticle suspensions, then particle size is reduced to nanoparticle range, but processing complexity and equipment requirements increase

Engineering Contradiction:

Improveparticle sizeVSAvoidprocessing equipment requirements

Core Design Contradiction:

Volume of moving objectVSDevice complexity

Solution Approach 1:

The patent replaces mechanical high-shear homogenization with a chemical/self-assembly approach where nanoparticles form spontaneously upon mixing lyophilized composition with aqueous buffer. This substitution eliminates the need for complex mechanical equipment while achieving the desired nanoparticle size through molecular self-organization rather than mechanical force.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If strict aseptic conditions are maintained during nanoparticle preparation, then sterility is ensured, but manufacturing complexity and cost increase

Engineering Contradiction:

ImprovesterilityVSAvoidmanufacturing process simplicity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent incorporates sterilizing agents and preservatives into the lyophilized nanoparticle composition before freezing. This preliminary action ensures sterility is built into the product formulation itself, allowing subsequent storage and handling under less stringent conditions while maintaining sterile status, thereby reducing manufacturing complexity.

Inventive Principle:

Principle #10Preliminary action

4Quantity of substance

If antigen loading capacity is increased on microparticle carriers, then immunogenicity is enhanced, but particle aggregation and suspension formation difficulties increase

Engineering Contradiction:

Improveantigen loading capacityVSAvoidsuspension stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the size parameter from microparticle to nanoparticle scale, which fundamentally alters the surface area to volume ratio. This parameter change enables high antigen loading capacity while maintaining suspension stability, as the increased surface area relative to volume provides more attachment sites for antigens without promoting aggregation that plagues larger microparticles.

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 nanoparticle compositions demonstrate enhanced immunogenicity, ease of preparation, and increased antigen loading capacity compared to microparticle technologies, facilitating effective immune responses with improved processing efficiency.

Implementation Method 1

sterile lyophilized nanoparticle compositions which comprise the following: at least one biodegradable polymer, at least one surfactant, at least one cryoprotective agent and at least one antigen

Methodology Applied

Scientific EffectLyophilization: Freeze Drying

Implementation Method 2

at least one cryoprotective agent

Methodology Applied

Scientific EffectCryoprotection:

Implementation Method 3

at least one surfactant

Methodology Applied

Scientific EffectSurfactant action: Surfactant

Data Source

PatentUS9393215B2Nanoparticles for use in immunogenic compositions

Publication Date: 2016.07.19 GLAXOSMITHKLINE BIOLOGICALS SA

AI summary

Disclosed herein are sterile-filtered lyophilized nanoparticle compositions which contain at least one biodegradable polymer, at least one surfactant, at least one cryoprotective agent and at least one antigen. Also disclosed are methods of making and using such compositions and kits supplying such compositions.