Water-in-oil emulsion for anticancer agent vectorization

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Solution Overview

Problem

Current anticancer agent delivery methods, particularly water-in-oil emulsions, face challenges with stability and effectiveness due to rapid release of the therapeutic agent into the bloodstream, leading to reduced tumor targeting and increased systemic toxicity, along with risks of embolism.

Innovation Solution

A water-in-oil emulsion composition comprising 20-40% aqueous phase with an anticancer agent and 60-80% iodized oil, stabilized by a surfactant of specific formula, which maintains stability for at least 24 hours and enhances vectorization capacity, reducing plasma concentration of the anticancer agent by over 90% within 5 minutes post-injection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If water-in-oil emulsion is used to deliver anticancer agent, then tumor targeting is improved, but stability is insufficient leading to rapid release into bloodstream

Engineering Contradiction:
Improvetumor targeting accuracyVSAvoidemulsion stability
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent modifies the chemical structure of the surfactant by varying the carbon chain lengths (R1: C16-C22, R2: C12-C18) and ethylene oxide units (m: 5-20) to optimize the HLB value between 3.5-6.5. This parameter optimization ensures the surfactant provides sufficient stability to prevent rapid drug release while maintaining the water-in-oil emulsion structure for accurate tumor targeting.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite emulsion system combining iodized oil (lipid phase), aqueous phase containing anticancer agent, and specifically designed nonionic surfactant. This composite formulation achieves both stability (preventing premature release) and tumor targeting capability, resolving the contradiction between these two requirements.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If high HLB surfactant is used to stabilize emulsion, then emulsion stability is improved, but droplet size increases causing embolism risk

Engineering Contradiction:
Improveemulsion stabilityVSAvoidembolism risk
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent precisely controls the HLB value of the surfactant within the narrow range of 3.5-6.5 by adjusting the carbon chain lengths and ethylene oxide units. This optimized HLB range provides sufficient emulsion stability while maintaining small droplet size (below embolism threshold), simultaneously achieving both stability and safety requirements.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If emulsion is prepared in advance for hospital use, then productivity is improved, but stability over time is compromised

Engineering Contradiction:
Improvepreparation efficiencyVSAvoidtemporal stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent enables advance preparation of the emulsion composition by providing a stable formulation that maintains its properties over time. The optimized surfactant system allows the emulsion to be prepared beforehand in hospital settings, improving workflow efficiency while maintaining stability throughout the required storage and usage period.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The specific surfactant parameters (HLB 3.5-6.5, controlled carbon chains and ethylene oxide units) provide enhanced temporal stability, allowing the emulsion to maintain its structural integrity and drug encapsulation over extended periods, thus enabling advance preparation without compromising stability.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3102214B1Composition for vectorizing an Anti-cancer agent
Publication Date: 2022.04.13 GUERBET SA
  • EP3102214B1 patent drawingFigure 1
  • EP3102214B1 patent drawingFigure 2
  • EP3102214B1 patent drawingFigure 3

AI summary

The invention relates to a stable water-in-oil emulsion composition containing: 20% to 40% (v/v) aqueous phase in the form of droplets and containing an anti-cancer agent; and 60% to 80% (v/v) lipid phase containing an iodized oil and at least one surfactant, having Formula (I), in a proportion, of surfactant mass relative to the total volume of the composition, of 0.3% to 5%, formula (I) for said surfactant being the following in which: s has a value of 0 or 1; m is a whole number from 2 to 30; R1 is a Formula (II) grouping wherein n is a whole number from 4 to 10, o is a whole number from 1 to 4, p is a whole number from 3 to 7; q is a whole number from 2 to 10, and r has a value of 0 or 1; R2 is a hydrogen atom or is identical to R1; and each R3 is, separately, a hydrogen atom or is identical to R1. The invention also relates to an emulsion obtained from said composition, to the preparing method thereof, and to the use thereof for treating cancer and the metastases thereof.