Cyclic Peptide Peptidesomes for Stable In Vivo Drug Delivery
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Solution Overview
Problem
Peptide-based vesicles, or peptidesomes, face challenges in maintaining structural stability and targeting efficiency in vivo due to differences in nanostructural properties between in vitro and in vivo conditions, leading to aggregation, cytotoxicity, and reduced targeting ability.
Innovation Solution
A cyclic peptide with a hydrophilic and hydrophobic peptide component linked by a linker, self-assembling into a peptidesome with a vesicular structure, allowing for targeted drug delivery and resistance to proteases, maintaining stability and avoiding aggregation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If peptide-based vesicles are used for drug delivery, then biocompatibility and structural diversity are improved, but structural stability and targeting efficiency deteriorate in vivo due to aggregation and protease sensitivity
Solution Approach 1:
The peptide is divided into distinct functional domains: hydrophobic core region for membrane insertion, hydrophilic region for solubility, and cell-penetrating peptide sequence for targeted delivery. This segmentation allows each region to perform its specific function independently, resolving the contradiction between structural diversity and stability.
Solution Approach 2:
The invention creates a composite structure by combining hydrophobic and hydrophilic peptide sequences in a single amphipathic molecule. This composite design enables the vesicle to maintain structural integrity in aqueous environments while preserving membrane interaction capabilities, thereby improving both biocompatibility and structural stability simultaneously.
2Stability of the object's composition
If peptides are made more hydrophilic to improve solubility, then aggregation is reduced, but membrane insertion capability and targeting ability deteriorate
Solution Approach 1:
Different regions of the peptide are assigned different hydrophobicity characteristics: the core region maintains hydrophobicity for membrane insertion, while the terminal regions are made hydrophilic for solubility. This local quality differentiation resolves the contradiction by allowing each region to optimize its function without compromising the other.
Solution Approach 2:
The invention optimizes the hydrophobicity-hydrophilicity balance by adjusting the length and composition of different peptide segments. By changing these parameters, the peptide achieves optimal solubility while maintaining sufficient hydrophobic character for effective membrane insertion and targeting.
3Quantity of substance
If peptide concentration is increased to improve drug loading capacity, then drug delivery efficiency is enhanced, but cytotoxicity increases
Solution Approach 1:
The cell-penetrating peptide acts as an intermediary that facilitates drug delivery at lower concentrations. By enhancing the efficiency of cellular uptake and intracellular delivery, the mediator allows reduced peptide dosing while maintaining effective drug loading capacity, thereby reducing cytotoxicity.
Solution Approach 2:
The amphipathic peptide structure enables self-assembly into vesicles that automatically organize drugs and deliver them to target cells. This self-service capability increases delivery efficiency without requiring high peptide concentrations, thus reducing cytotoxic effects.
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 cyclic peptide-based peptidesome achieves stable drug delivery directly into cancer cells, providing superior drug efficacy and resistance to proteases, with enhanced intracellular delivery efficiency and reduced cytotoxicity.
Implementation Method 1
Amino acids or peptides that constitute a protein tend to 'self-assemble' to form specific structures and shapes. Interests in self-assembled peptide nanostructures (SPNs) have been escalated in recent years.
Implementation Method 2
a hydrophobic peptide represented by General Formula 1
Implementation Method 3
a hydrophilic peptide consisting of 2 to 12 L- or D-arginine residues
Implementation Method 4
the peptidesome membrane disrupts, allowing for direct intracellular delivery without passing through endosomes
Implementation Method 5
with enhanced intracellular delivery efficiency and reduced cytotoxicity
Data Source
AI summary
The present disclosure relates to a novel cyclic peptide based on nano-biostructural control, a peptidesome with a core/shell structure including the same, and a use thereof. The cyclic peptide of the present disclosure may be prepared into a peptidesome having a vesicular structure consisting of a hollow core and a bilayer shell through self-assembly in a liquid. Since the prepared peptidesome is stable not only in vitro but also in vivo, especially against proteases in vivo, it can be usefully used as a drug carrier.