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

Abstract

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.

Biomineral-Based Composite Materials in Regenerative Medicine

“…The field of biomimetic silica formation has been becoming increasingly intriguing due to its potential to utilize gentle reaction conditions, control the silica structure, and facilitate relatively simple cargo loading [ 74 ]. The advancement of bio-inspired and biomimetic silica formation has been fueled by the identification of the molecules involved in natural silica biomineralization processes like silaffin peptides and polyamines [ 35 , 75 , 76 , 77 , 78 ].…”

“…These Silica/Fn-SFP nanoparticles exhibited high drug-loading capacities along with pH-responsive drug release patterns and a dual DDS [ 232 ]. Leveraging this biocompatible framework, a dual DDS was developed, capable of concurrently administering anticancer drugs and any other type of drug, such as antibiotics, thus effectively combating cancer and microbial infections [ 35 , 233 , 234 ].…”

“…[ 34 ] with permission from © 2024 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. ( iv ) Self-entrapment of antimicrobial peptide CPP-KR12 in silica matrix through CPP-KR12-mediated silica deposition [ 35 ] (CC By 4.0). ( c ) ( i ) The formation processes and mechanisms of human hard tissues, including bones and teeth [ 36 ] (CC By 4.0) with permission from Copyright © 2024, The Author(s).…”

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

“…AMPs predominantly target the bacterial cell membrane through electrostatic interactions, leading to membrane disruption via destabilization, changes in fluidity, and depolarization. This action is facilitated by the amphipathic nature of AMPs, which possess a balance of cationic and non-polar residues [ 16 ]. Unlike traditional antibiotics, which often target specific cellular processes and risk inducing resistance, the broad and nonspecific mode of action of AMPs makes it difficult for pathogens to develop resistance [ 17 ].…”