Research Article

Conformationally restricted, dipeptide-based, self-assembled nanoparticles for efficient vancomycin delivery

Nitin Yadav^‡

Utkarsh Kumar^‡

Virander Singh Chauhan

Molecular Medicine Group, International Centre for Genetic Engineering & Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India

Delhi Institute of Pharmaceutical Sciences & Research, Mehrauli-Badarpur Road, Sector-3, Pushpvihar, New Delhi, 110017, India

‡These authors contributed equally to this work

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Utkarsh Kumar^‡

https://orcid.org/0000-0001-9875-9549

Molecular Medicine Group, International Centre for Genetic Engineering & Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India

‡These authors contributed equally to this work

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Virander Singh Chauhan

*Author for correspondence:

E-mail Address: virander@icgeb.res.in

https://orcid.org/0000-0001-9875-9549

Molecular Medicine Group, International Centre for Genetic Engineering & Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India

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Published Online:16 Jan 2023https://doi.org/10.2217/nnm-2022-0144

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Abstract

Aim: Emergence of vancomycin (Van) resistance, and usage of its higher dose and short half-life are posing a serious concern. Slow and sustained release of Van using a nanodelivery system may overcome these problems. Materials & methods: Arginine-α,β-dehydrophenylalanine (RΔF) was synthesized using solution-phase synthesis which self-assembled into nanospheres. Van was entrapped in the nanoparticles (NPs). In vitro and in vivo efficacy of Van-RΔF was determined using broth microdilution and the mouse thigh infection model, respectively. Results & conclusion: Van-RΔF NPs efficiently inhibited bacterial growth (Staphylococcus aureus), while Van alone showed limited growth inhibition in in vitro. Intravenous administration of Van-RΔF in mice with bacterial thigh infection showed enhanced efficacy (double) compared with Van alone, which indicates its high potential for further development.

Plain language summary

Currently, microbial infections have become the most prevalent threat to human health. In the past few decades, researchers have tried different strategies to deal with these infections by developing new antimicrobial agents and/or improving the efficacy of already available antimicrobial agents. Controlled delivery of antimicrobial agents using nanosized vehicle systems has shown great promise in antimicrobial therapy. The authors have developed an ultrashort, modified, peptide-based nanoparticle system that can load vancomycin and release it in a controlled and sustained manner. Unlike other polymer-based nanoparticles, these dipeptide-based nanoparticles are easy to synthesize and highly biocompatible in nature. Vancomycin delivered via these peptide-based nanoparticles showed higher antibacterial activity than the drug alone. These results clearly indicated the high potential of this nanoformulation for further development as a delivery vehicle system for efficient antimicrobial therapy.

Keywords:

Papers of special note have been highlighted as: • of interest

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Vol. 17, No. 26

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Received 7 June 2022

Accepted 16 December 2022

Published online 16 January 2023

Published in print November 2022

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2022-0144

Acknowledgments

The authors thank GH Rajacharya and T Choedon at ICGEB (New Delhi, India), for helping them with mass spectrometry and TEM analysis. The authors also thank S Chaturvedi for assistance in performing in vivo experiments.

Financial & competing interests disclosure

The authors acknowledge the Department of Biotechnology (DBT, grant nos. BT/HRD/35/07/VSC/2015 and BT/PR31130/MED/15/197/2019), Centre for Cellular and Molecular Platforms (C-Camp) and Biotechnology Ignition Grant (BIG) and Biotechnology Industry Research Assistance Council (BIRAC) for financial support (grant nos. BIRAC/CCAMP0770/BIG-13/18, BT/AIR0809/PACE-18/19 and BT/CRS0167/CRS-08/15). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

BALB/c mice were housed in the animal house facility of the International Centre for Genetic Engineering and Biotechnology (New Delhi, India), under a pathogen-free environment. All procedures were approved by the Institutional Animal Care and Use Committee (approval number: ICGEB/IAEC/07032020/VSC-3).

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