Transdermal Peptide Nuclear Localization for Macromolecule Delivery
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Solution Overview
Problem
Current transdermal penetration enhancers have limitations in effectively delivering biological macromolecules, such as proteins, across the skin due to their short duration, susceptibility to metabolization, skin toxicity, and inability to penetrate macromolecular substances, particularly those with molecular weights greater than 500 Da, posing challenges in treating diseases through the epidermal route.
Innovation Solution
A transdermal peptide with nuclear localization ability, specifically synthesized with an amino acid sequence of SEQ ID NO: 1, capable of autonomously entering eukaryotic cells and localizing in the nucleus, facilitating the transdermal penetration of macromolecular proteins and therapeutic drugs, including fusion proteins linked to fluorescent markers, to treat skin diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If transdermal penetration enhancers are used to accelerate drug penetration through the skin, then the penetration speed is improved, but the duration of action is short and they are susceptible to metabolization
Solution Approach 1:
The patent uses a specific peptide sequence (SEQ ID NO: 1) as an intermediary mediator that facilitates transdermal penetration of macromolecules. This peptide acts as a carrier that temporarily binds to the macromolecular substance, enabling it to cross the stratum corneum barrier and enter cells, thereby resolving the contradiction between achieving fast penetration and maintaining sustained action.
2Reliability
If transdermal penetration enhancers are used to improve penetration, then the penetration ability is enhanced, but skin toxicity occurs at high concentrations
Solution Approach 1:
The patent changes the chemical parameters by using a specifically designed peptide sequence (SEQ ID NO: 1) with particular amino acid composition and structure. This peptide achieves effective transdermal penetration at low concentrations without the high concentration requirements that cause skin toxicity in conventional penetration enhancers, thus resolving the contradiction between penetration ability and skin safety.
3Reliability
If physical methods such as ultrasonic method, electric shock, and microneedle are used for transdermal penetration, then the penetration of macromolecules is improved, but the dependence on equipment makes large-scale application difficult
Solution Approach 1:
The patent replaces complex mechanical and physical systems (ultrasonic devices, electric shock equipment, microneedle apparatus) with a chemical solution - a specifically designed peptide sequence (SEQ ID NO: 1). This peptide mediates transdermal penetration through biochemical interactions rather than mechanical force, eliminating equipment dependence and enabling simple, scalable application while maintaining effective macromolecule penetration.
4Reliability
If conventional transdermal penetration enhancers are used, then penetration of small molecules is improved, but they have little effect on transdermal penetration of biological macromolecules such as proteins
Solution Approach 1:
The patent designs a universal peptide sequence (SEQ ID NO: 1) that can mediate transdermal penetration for multiple types of substances including both small molecules and biological macromolecules such as proteins. This single peptide structure exhibits multi-functional capability, binding to and facilitating the transport of diverse macromolecular substances through the skin barrier, thereby achieving universality across different molecular sizes and types.
5Reliability
If peptides with nuclear localization ability are developed, then the ability to deliver molecules to the nucleus is improved, but there are no reports of peptides with both nuclear localization and transdermal penetration abilities
Solution Approach 1:
The patent merges two previously separate functions into a single peptide sequence (SEQ ID NO: 1): transdermal penetration capability and nuclear localization signal. This combined peptide structure first facilitates the transdermal penetration of macromolecules into cells, and then directs these macromolecules to the nucleus through its nuclear localization signal, achieving both functions simultaneously in one molecule.
Data Source
AI summary
A transdermal peptide with a nuclear localization ability and having an amino acid sequence as shown in SEQ ID NO: 1 is disclosed. A fusion protein including a macromolecular protein with one end being linked to the transdermal peptide is also disclosed. The transdermal peptide can be used in the preparation of a medicament or a transdermal preparation for treating skin diseases. A medicament for treating a skin disease includes the transdermal peptide and a pharmaceutically acceptable excipient. The transdermal peptide enters the cells autonomously to locate in the nuclei, and can penetrate through the stratum corneum of the skin into cells in the dermis. The peptide is conveniently synthesized artificially and suitable for transdermal administration, and has a therapeutic potential via transdermal administration by carrying a drug for treating skin diseases.