Microalgae Extracellular Vesicle Isolation for Scalable Drug Delivery

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Solution Overview

Problem

The prior art lacks a method for isolating extracellular vesicles from microalgae, which are potentially advantageous as natural carriers for drug delivery due to their high growth rates, sustainable origin, and societal acceptance, but their secretion mechanisms were not previously known, and existing methods from other sources face challenges like liver accumulation, limited scalability, and toxicity.

Innovation Solution

A novel method for isolating extracellular vesicles from photosynthetic, non-fermenting microalgae, involving inoculation, cultivation, and differential centrifugation steps to obtain Alix-positive EVs at specific densities, allowing large-scale production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If extracellular vesicles are isolated from mammalian cells for drug delivery, then therapeutic delivery capability is improved, but liver accumulation and toxicity occur

Engineering Contradiction:

Improvetherapeutic delivery capabilityVSAvoidliver accumulation and toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses microalgal extracellular vesicles as a natural copy/alternative to mammalian cell-derived EVs. Both types of EVs share similar structural characteristics (lipid bilayer membrane, size range, ability to carry therapeutic agents), but microalgal EVs avoid the immunogenicity and liver accumulation issues associated with mammalian sources, providing a safer biocompatible alternative

Inventive Principle:

Principle #26Copying

Solution Approach 2:

Microalgae can be rapidly cultivated and harvested to produce extracellular vesicles on a large scale. The microalgal biomass serves as a renewable, sustainable source that can be continuously produced without the ethical and scalability limitations of mammalian cell cultures, providing an abundant supply of biocompatible nanocarriers

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Reliability

If extracellular vesicles are produced from human or bovine cells, then nanocarrier functionality is achieved, but scalability and production yield are limited

Engineering Contradiction:

Improvenanocarrier functionalityVSAvoidscalability and production yield

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

Microalgae serve multiple functions: they are photosynthetic organisms that can be cultivated in various conditions, produce extracellular vesicles with therapeutic delivery capability, and can be scaled up from laboratory to industrial production. This universality allows the same organism to fulfill both the functional requirement of producing effective nanocarriers and the productivity requirement of large-scale manufacturing

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent optimizes cultivation parameters (light intensity, temperature, nutrient composition, pH) and extraction parameters (centrifugation speed, buffer composition, pH adjustment) to maximize EV yield from microalgae. By systematically adjusting these parameters, the method achieves high productivity while maintaining the functional integrity of the extracellular vesicles

Inventive Principle:

Principle #35Parameter changes

3Productivity

If a novel isolation method for microalgal EVs is developed, then sustainable sourcing and high yield are achieved, but method complexity increases

Engineering Contradiction:

Improvehigh yield and sustainable sourcingVSAvoidisolation method complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The isolation method is divided into distinct sequential steps: (1) microalgal cultivation and EV secretion, (2) cell removal by centrifugation, (3) EV concentration by ultracentrifugation or filtration, and (4) EV purification and characterization. This segmentation allows each step to be optimized independently and facilitates scale-up from small to large volumes without proportionally increasing complexity

Inventive Principle:

Principle #1Segmentation

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 method enables the production of microalgae-derived EVs suitable for molecular delivery of diagnostic, therapeutic, and cosmetic agents, overcoming scalability and toxicity issues of mammalian-derived EVs, with high yield and sustainable sourcing.

Implementation Method 1

differential centrifugation steps to obtain Alix-positive EVs at specific densities

Methodology Applied

Scientific EffectCentrifugal separation: Centrifugal Separation

Data Source

PatentUS12584095B2Extracellular vesicles from microalgae

Publication Date: 2026.03.24 CONSIGLIO NAT DELLE RICERCHE

AI summary

Extracellular vesicles derived from native, photosynthetic, non-fermenting microalgae are provided. A method for isolating extracellular vesicles from native, photosynthetic, non-fermenting microalgae involving growth, centrifugation and ultracentrifugation steps is also provided. Use of the isolated extracellular vesicles as carriers for delivering diagnostic, therapeutic, nutraceutic and/or cosmetic agents is further provided.