C16-Acylated Lactoferrin Peptide Nanoparticles for Cellular Uptake

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Solution Overview

Problem

Current nanoparticles based on bio-resorbable polyesters and hydrophilic polymers with non-acylated or differently acylated human lactoferrin-derived peptides are less effective in facilitating the uptake of active pharmaceutical ingredients by cells, as evidenced by lower relative fluorescence in cell uptake studies.

Innovation Solution

A nanoparticle comprising a bio-resorbable polyester and hydrophilic polymer core coated with a C16-acylated human lactoferrin-derived peptide, specifically with the sequence KCFQWQRNMRKVRGPPVSCIKR or a sequence differing by no more than 8 amino acid positions, which enhances cellular uptake of active ingredients by promoting cell penetration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If non-acylated or differently acylated human lactoferrin-derived peptides are used as nanoparticle coating, then the nanoparticle structure is simpler and manufacturing is easier, but cellular uptake efficiency and bioavailability are reduced

Engineering Contradiction:

Improvenanoparticle coating applicationVSAvoidcellular uptake efficiency

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying the acylation state of the lactoferrin-derived peptide coating. Specifically, using C16-acylated peptides (with long-chain fatty acid modification) instead of non-acylated or short-chain acylated variants changes the physicochemical properties of the nanoparticle surface, enhancing cellular uptake efficiency while maintaining manufacturing feasibility

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by combining the bio-resorbable polyester core with hydrophilic polymer and C16-acylated human lactoferrin-derived peptide coating. This composite structure integrates the biodegradability of polyester, the hydrophilicity of polymer, and the cell-penetrating capability of acylated peptides, achieving both ease of manufacture and high cellular uptake efficiency

Inventive Principle:

Principle #40Composite materials

2Reliability

If C16-acylated human lactoferrin-derived peptide coating is applied to enhance cellular uptake, then bioavailability and delivery efficiency are improved, but nanoparticle manufacturing complexity increases

Engineering Contradiction:

ImprovebioavailabilityVSAvoidnanoparticle structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by concentrating the functional enhancement to the surface coating layer rather than modifying the entire nanoparticle structure. The C16-acylated peptide coating provides localized cell-penetrating functionality at the nanoparticle surface, while the core structure remains relatively simple and manufacturable

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs preliminary action by pre-acylating the lactoferrin-derived peptide with C16 fatty acid chains before nanoparticle formulation. This pre-modification ensures consistent cell-penetrating activity and simplifies the overall manufacturing process by eliminating the need for post-synthesis acylation steps

Inventive Principle:

Principle #10Preliminary action

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 C16-acylated human lactoferrin-derived peptide coating significantly improves the relative fluorescence and cellular uptake of nanoparticles, particularly in A549 lung carcinoma cells, compared to nanoparticles with non-acylated or differently acylated peptides, indicating enhanced bioavailability and delivery efficiency.

Implementation Method 1

Human lactoferrin-derived peptides (hLFF) may generally show a biological cell penetrating function (cell penetrating peptide (CPP)) which means when delivered simultaneously with an active pharmaceutical ingredient (API) to human cells the human lactoferrin-derived peptides facilitates and promotes the uptake of the API in the cells

Methodology Applied

Scientific EffectCell penetration:

Implementation Method 2

The C16-acylated human lactoferrin-derived peptide coating significantly improves the relative fluorescence and cellular uptake of nanoparticles, particularly in A549 lung carcinoma cells

Methodology Applied

Scientific EffectCellular uptake: Absorption (physical)

Data Source

PatentEP3790534B1Nanoparticle comprising a bio-resorbable polyester, a hydrophilic polymer and an acylated human lactoferrin-derived peptide

Publication Date: 2023.08.30 EVONIK OPERATIONS GMBH

AI summary

The invention is concerned with a nanoparticle comprising a core, comprising a bio-resorbable polyester and a hydrophilic polymer, wherein the hydrophilic polymer is a portion of the bio-resorbable polyester or a separate polymer, and, onto the core, an acylated human lactoferrin- derived peptide, wherein the acylated human lactoferrin-derived peptide is a peptide with the amino acid sequence SEQ ID No.1: KCFQWQRNMRKVRGPPVSCIKR or an amino acid sequence, which does not differ by more than 8 amino acid positions from the sequence SEQ.ID.No.1 and wherein the N-terminus of the human lactoferrin-derived peptide is acylatedwith a C16-monoacyl group.