PHHP Peptide Carrier Membrane Delivery

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Solution Overview

Problem

Current methods for delivering therapeutic and diagnostic agents across biological membranes are inefficient due to the hydrophilic and large size of macromolecules and small molecules, leading to limited bioavailability and toxicity issues with existing cell penetration peptides.

Innovation Solution

Development of a novel peptide design, Positive-Helix-Hydrophobic Peptides (PHHP) with an amphipathic beta strand-turn-alpha helix motif domain, which facilitates membrane attachment, entry, and passage while reducing toxicity and forming nano- and micro-structures for enhanced delivery of macromolecules and small molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional carriers or peptides are used to deliver macromolecules across biological membranes, then delivery mechanism is provided, but delivery efficiency is poor and toxicity occurs

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidtoxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the physicochemical parameters of cell penetration peptides by incorporating specific amino acid sequences (e.g., TAT, penetratin, arginine-rich peptides) with optimized charge, hydrophobicity, and molecular weight to enhance membrane permeation while reducing toxicity. The peptides are designed with specific sequences that interact with membrane lipids and proteins to facilitate efficient transmembrane transport of macromolecules.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite delivery systems by conjugating cell penetration peptides with macromolecular carriers (proteins, nucleic acids, polysaccharides) and incorporating these into various delivery platforms including liposomes, micelles, and nanoparticles. This composite approach combines the membrane-permeating capability of peptides with the cargo-carrying capacity of macromolecular carriers.

Inventive Principle:

Principle #40Composite materials

2Reliability

If the size and hydrophilicity of molecules increase, then therapeutic activity is improved, but membrane crossing capability deteriorates

Engineering Contradiction:

Improvetherapeutic activityVSAvoidmembrane crossing capability

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent employs cell penetration peptides as intermediary molecules that bridge the gap between hydrophilic macromolecular therapeutics and the hydrophobic plasma membrane. These peptide intermediaries interact with both the polar surface of macromolecules and the nonpolar lipid bilayer, facilitating the transport of large, hydrophilic molecules across the membrane barrier through mechanisms including direct permeation, endocytosis, and membrane pore formation.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Ease of operation

If existing cell penetration peptides are used, then some membrane crossing is achieved, but toxicity and limited bioavailability occur

Engineering Contradiction:

Improvemembrane crossingVSAvoidbioavailability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent designs cell penetration peptides with specific local structural and chemical properties, including positively charged amino acid residues, hydrophobic regions, and specific sequences (e.g., TAT from HIV, penetratin from human melanoma) that are optimized for interacting with specific membrane components. This local optimization enables selective membrane crossing in target tissues while minimizing off-target effects and toxicity.

Inventive Principle:

Principle #3Local quality

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 PHHP peptides demonstrate improved intracellular uptake and transmembrane delivery of therapeutic agents, such as human alpha crystallin B and human lens epithelium-derived growth factor, with reduced toxicity and prolonged retention at target sites, enhancing the delivery of both proteins and small molecule solutes across various cellular and tissue barriers.

Implementation Method 1

The primary lipid component is very hydrophobic in nature... a novel peptide design, Positive-Helix-Hydrophobic Peptides (PHHP) with an amphipathic beta strand-turn-alpha helix motif domain, which facilitates membrane attachment, entry, and passage

Methodology Applied

Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 2

PHHP peptides with an amphipathic beta strand-turn-alpha helix motif domain... amphipathic beta strand-turn-alpha helix (PTa) motif domains

Methodology Applied

Scientific EffectAmphipathic structure: Amphiphiles

Data Source

PatentUS20240092837A1Novel Peptide Carrier Compositions

Publication Date: 2024.03.21 THE REGENTS OF THE UNIVERSITY OF COLORADO

AI summary

The present invention describes peptides, peptides carriers, peptide nanobodies, and peptide-drug covalent conjugates having efficient cell and tissue penetration. The peptides and associated configurations can be used in covalent attachments or as complexes or nanoparticles in conjunction with therapeutic agents to enhance their tissue, cellular, and intracellular delivery. Also, the peptides and associated configurations can enhance binding to negatively charged matrices in the body for improved localization or retention of therapeutic carriers and agents.