Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their vulnerability to protease degradation and toxicity towards mammalian cells has hindered their clinical application. To overcome these challenges, our stu...

Full description

Bibliographic Details
Main Authors: Mi-Ran Ki, Sung Ho Kim, Tae In Park, Seung Pil Pack
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/22/16423
_version_ 1797459021789134848
author Mi-Ran Ki
Sung Ho Kim
Tae In Park
Seung Pil Pack
author_facet Mi-Ran Ki
Sung Ho Kim
Tae In Park
Seung Pil Pack
author_sort Mi-Ran Ki
collection DOAJ
description Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their vulnerability to protease degradation and toxicity towards mammalian cells has hindered their clinical application. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs applicable to effective drug–device combination products. The KR12 antimicrobial peptide was chosen, and in order to further enhance its delivery and efficacy the human immunodeficiency virus TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica particles with self-entrapped CPP-KR12 peptide using biomimetic silica precipitability because of its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was observed at a slightly delivered rate, with improved stability against trypsin treatment and a reduction in cytotoxicity compared to CPP-KR12. Finally, the antimicrobial potential of the CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated. CPP-KR12 is coated in the form of submicron-sized particles on the surface of the BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug–device combination product for tissue regeneration.
first_indexed 2024-03-09T16:45:31Z
format Article
id doaj.art-f56ab03b46b0439d82c8900c34dc49ac
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-09T16:45:31Z
publishDate 2023-11-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-f56ab03b46b0439d82c8900c34dc49ac2023-11-24T14:47:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221642310.3390/ijms242216423Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery SystemMi-Ran Ki0Sung Ho Kim1Tae In Park2Seung Pil Pack3Department of Biotechnology and Bioinformatics, Korea University, Sejong-ro 2511, Sejong 30019, Republic of KoreaDepartment of Biotechnology and Bioinformatics, Korea University, Sejong-ro 2511, Sejong 30019, Republic of KoreaDepartment of Biotechnology and Bioinformatics, Korea University, Sejong-ro 2511, Sejong 30019, Republic of KoreaDepartment of Biotechnology and Bioinformatics, Korea University, Sejong-ro 2511, Sejong 30019, Republic of KoreaAntimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their vulnerability to protease degradation and toxicity towards mammalian cells has hindered their clinical application. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs applicable to effective drug–device combination products. The KR12 antimicrobial peptide was chosen, and in order to further enhance its delivery and efficacy the human immunodeficiency virus TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica particles with self-entrapped CPP-KR12 peptide using biomimetic silica precipitability because of its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was observed at a slightly delivered rate, with improved stability against trypsin treatment and a reduction in cytotoxicity compared to CPP-KR12. Finally, the antimicrobial potential of the CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated. CPP-KR12 is coated in the form of submicron-sized particles on the surface of the BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug–device combination product for tissue regeneration.https://www.mdpi.com/1422-0067/24/22/16423antimicrobial peptidecell penetrating peptidesilica forming peptidebiomimetic silica depositiondrug deliverydrug device combination
spellingShingle Mi-Ran Ki
Sung Ho Kim
Tae In Park
Seung Pil Pack
Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System
International Journal of Molecular Sciences
antimicrobial peptide
cell penetrating peptide
silica forming peptide
biomimetic silica deposition
drug delivery
drug device combination
title Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System
title_full Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System
title_fullStr Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System
title_full_unstemmed Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System
title_short Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System
title_sort self entrapment of antimicrobial peptides in silica particles for stable and effective antimicrobial peptide delivery system
topic antimicrobial peptide
cell penetrating peptide
silica forming peptide
biomimetic silica deposition
drug delivery
drug device combination
url https://www.mdpi.com/1422-0067/24/22/16423
work_keys_str_mv AT miranki selfentrapmentofantimicrobialpeptidesinsilicaparticlesforstableandeffectiveantimicrobialpeptidedeliverysystem
AT sunghokim selfentrapmentofantimicrobialpeptidesinsilicaparticlesforstableandeffectiveantimicrobialpeptidedeliverysystem
AT taeinpark selfentrapmentofantimicrobialpeptidesinsilicaparticlesforstableandeffectiveantimicrobialpeptidedeliverysystem
AT seungpilpack selfentrapmentofantimicrobialpeptidesinsilicaparticlesforstableandeffectiveantimicrobialpeptidedeliverysystem