Citrate-Coated Cerium Oxide Nanoparticles for Posterior Eye Delivery

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current treatments for ocular diseases of the posterior segment, such as age-related macular degeneration and diabetic retinopathy, face challenges due to the ocular barriers that hinder drug delivery, leading to low efficacy and significant side effects from intravitreal injections, especially in early stages of the diseases.

Innovation Solution

Development of citrate-coated single-crystal cerium oxide nanoparticles with a diameter of 3 to 5 nm, which are administered topically and remain in colloidal suspension to penetrate the anterior segment and reach the posterior segment without aggregation, avoiding the need for functionalization or encapsulation, thus providing a less invasive alternative to intravitreal injections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If intravitreal injection is used to treat posterior segment diseases, then drug delivery efficacy is improved, but side effects and invasiveness increase

Engineering Contradiction:
Improvedrug delivery efficacyVSAvoidside effects and invasiveness
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses citrate-coated cerium oxide nanoparticles as an intermediary carrier that mediates drug delivery from the topical surface to the posterior segment. The nanoparticles serve as a bridge, transporting therapeutic agents across the ocular barriers without requiring direct intravitreal injection, thus maintaining delivery efficacy while reducing invasiveness and side effects.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical intrusion method of intravitreal injection with a passive topical application system. Instead of mechanically penetrating the eye using needles, the nanoparticles are applied topically and naturally penetrate through ocular barriers via diffusion and endocytosis, substituting a non-invasive chemical/physical process for a traumatic mechanical one.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If topical administration is used to avoid ocular barriers, then invasiveness is reduced, but drug delivery to posterior segment fails

Engineering Contradiction:
ImproveinvasivenessVSAvoiddrug delivery to posterior segment
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent changes the physical and chemical parameters of the delivery system by using nanoscale cerium oxide particles (3-5 nm) coated with citrate. This nanosization and surface modification enables the particles to penetrate ocular barriers that would block larger molecules, transforming the delivery mechanism to achieve posterior segment penetration while maintaining topical application simplicity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite nanoparticle system combining cerium oxide core with citrate coating. This composite structure provides both the penetrating capability of the nanoscale core and the biocompatibility/surface properties of the citrate coating, enabling successful navigation through ocular barriers while maintaining safety and efficacy.

Inventive Principle:
Principle #40Composite materials

3Length of moving object

If nanoparticle size is reduced to enhance penetration, then barrier penetration is improved, but aggregation and precipitation occur

Engineering Contradiction:
Improvenanoparticle sizeVSAvoidcolloidal suspension stability
Core Design Contradiction:
Length of moving objectVSStability of the object's composition

Solution Approach 1:

Citrate molecules act as an intermediary coating on the nanoparticle surface, preventing direct nanoparticle-nanoparticle interactions that would lead to aggregation. The citrate layer serves as a steric barrier that maintains colloidal stability even at nanoscale dimensions, allowing the particles to remain dispersed and penetrate barriers effectively without precipitating.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Reliability

If functionalization or encapsulation is applied to nanoparticles, then penetration capability is improved, but device complexity increases

Engineering Contradiction:
Improvepenetration capabilityVSAvoidnanoparticle modification complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the need for complex functionalization and encapsulation steps by relying on the inherent properties of citrate-coated cerium oxide nanoparticles. The citrate coating naturally provides the necessary surface properties for penetration without requiring additional functional groups, peptides, or encapsulating shells, thus achieving penetration capability while minimizing complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

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

These nanoparticles achieve effective concentrations in the posterior segment with reduced toxicity and prolonged administration schedules, offering a safer and more effective treatment option for ocular diseases by maintaining therapeutic levels without systemic accumulation.

Implementation Method 1

citrate-coated single-crystal cerium oxide nanoparticles with a diameter of 3 to 5 nm, which are administered topically and remain in colloidal suspension to penetrate the anterior segment and reach the posterior segment without aggregation

Methodology Applied
Scientific EffectColloidal suspension: Colloid

Implementation Method 2

Even in case a drug can reach the posterior segment of the eye, it may be removed from the vitreous cavity through diffusion into the anterior chamber

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP4322968B1Ophthalmic topical composition with ceria nanoparticles for treating diseases of posterior segment of the eye
Publication Date: 2025.03.19 FUNDACIÓ HOSPITAL UNIVERSITARI VALL D HEBRON - INSTITUT DE RECERCA
  • EP4322968B1 patent drawingFigure 1~2
  • EP4322968B1 patent drawingFigure 3(A)~3(C)
  • EP4322968B1 patent drawingFigure 4~5

AI summary

Present invention relates to colloidal suspension of single crystal cerium oxide nanoparticles for use in the treatment of a disorder or disease of the posterior segment of the eye, said treatment comprising administration of a topical ophthalmic dose of the colloidal suspension. Invention also includes particular new eye drop suspensions.