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Nanotechnology-Based Delivery Systems for Antimicrobial Peptides.

ABSTRACT: Antimicrobial resistance (AMR) is a significant threat to global health. The conventional antibiotic pool has been depleted, forcing the investigation of novel and alternative antimicrobial strategies. Antimicrobial peptides (AMPs) have shown potential as alternative diagnostic and therapeutic agents in biomedical applications. To date, over 3000 AMPs have been identified, but only a fraction of these have been approved for clinical trials. Their clinical applications are limited to topical application due to their systemic toxicity, susceptibility to protease degradation, short half-life, and rapid renal clearance. To circumvent these challenges and improve AMP's efficacy, different approaches such as peptide chemical modifications and the development of AMP delivery systems have been employed. Nanomaterials have been shown to improve the activity of antimicrobial drugs by providing support and synergistic effect against pathogenic microbes. This paper describes the role of nanotechnology in the targeted delivery of AMPs, and some of the nano-based delivery strategies for AMPs are discussed with a clear focus on metallic nanoparticle (MNP) formulations.

SUBMITTER: Fadaka AO

PROVIDER: S-EPMC8620809 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Nanotechnology-Based Delivery Systems for Antimicrobial Peptides.

Fadaka Adewale Oluwaseun AO Sibuyi Nicole Remaliah Samantha NRS Madiehe Abram Madimabe AM Meyer Mervin M

Pharmaceutics 20211026 11

Antimicrobial resistance (AMR) is a significant threat to global health. The conventional antibiotic pool has been depleted, forcing the investigation of novel and alternative antimicrobial strategies. Antimicrobial peptides (AMPs) have shown potential as alternative diagnostic and therapeutic agents in biomedical applications. To date, over 3000 AMPs have been identified, but only a fraction of these have been approved for clinical trials. Their clinical applications are limited to topical appl ...[more]

PMID: 34834210

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Project description:BackgroundPlatinum resistance is a major challenge in the management of ovarian cancer. Even low levels of acquired resistance at the cellular level lead to impaired response to cisplatin. In ovarian cancer intraperitoneal therapy, nanoparticle formulation can improve the cisplatin's pharmacokinetics and safety profile.PurposeThis work aimed to investigate the chemo-sensitivity of ovarian cancer SKOV3 cells upon short-term (72h) single treatment of cisplatin and cisplatin-loaded biodegradable nanoparticles (Cis-NP). The aim was then to determine the therapeutic properties of Cis-NP in vivo using a SKOV3-luc cells' xenograft model in mice.MethodsCell cytotoxicity was assessed after the exposure of the cell culture to cisplatin or Cis-NP. The effect of treatments on EMT and CSC-like phenotype was studied by analyzing a panel of markers by flow cytometry. Intracellular platinum concentration was determined by inductively coupled plasma mass spectrometry (ICS-MS), and gene expression was evaluated by RNAseq analysis. The efficacy of intraperitoneal chemotherapy was evaluated in a SKOV3-luc cells' xenograft model in mice, through a combination of bioluminescence imaging, histological, and immunohistochemical analyses.ResultsWe observed in vitro that short-term treatment of cisplatin has a critical role in determining the potential induction of chemoresistance, and a nanotechnology-based drug delivery system can modulate it. The RNAseq analysis underlines a protective effect of nanoparticle system according to their ability to down-regulate several genes involved in chemoresistance, cell proliferation, and apoptosis. The highest intracellular platinum concentration obtained with Cis-NP treatment significantly improved the efficacy. Consistent with in vitro results, we found that Cis-NP treatment in vivo can significantly reduce tumor burden and aggressiveness compared to the free drug.ConclusionNanoparticle-mediated cisplatin delivery may serve as an intracellular depot impacting the cisplatin pharmacodynamic performance at cellular levels. These features may contribute to improving the drawbacks of conventional intraperitoneal therapy, and therefore will require further investigations in vivo.

Dataset Information

Nanotechnology-Based Delivery Systems for Antimicrobial Peptides.

Publications

Nanotechnology-Based Delivery Systems for Antimicrobial Peptides.

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