Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 9 October 2023 / Approved: 9 October 2023 / Online: 10 October 2023 (05:47:59 CEST)
Version 2 : Received: 10 October 2023 / Approved: 11 October 2023 / Online: 11 October 2023 (10:07:40 CEST)

A peer-reviewed article of this Preprint also exists.

Ki, M.-R.; Kim, S.H.; Park, T.I.; Pack, S.P. Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System. Int. J. Mol. Sci. 2023, 24, 16423. Ki, M.-R.; Kim, S.H.; Park, T.I.; Pack, S.P. Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System. Int. J. Mol. Sci. 2023, 24, 16423.

Abstract

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. 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. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of 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.

Keywords

antimicrobial peptide; cell penetrating peptide; silica forming peptide; biomimetic silica deposition; drug delivery; drug device combination

Subject

Chemistry and Materials Science, Biomaterials

Comments (1)

Comment 1
Received: 11 October 2023
Commenter: Miran Ki
Commenter's Conflict of Interests: Author
Comment: In section 2.1.1, reference #17 was added before reference #32, and reference #33 was replaced with a content-appropriate reference.

In Section 2.1.3, the peptide concentrations in the text below Figure 2 were not properly labeled and have been corrected to micromolar (µM).

In Section 2.2, Figure 3a, Figure 3b, and Figure 3c have been corrected to Figure 4a, Figure 4b, and Figure 4c, respectively.

Replace "Cpp" with "CPP" throughout the paper.

In Section 2.5, we have included Figure 8c in the relevant part of the text description.

In Section 3.11, we have removed the last sentence.
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