Controlled delivery of nikkomycin by PEG coated PLGA nanoparticles inhibits chitin synthase to prevent growth of Aspergillus flavus and Aspergillus fumigatus

Kamal Mayattu; Vandana Ghormade

doi:10.1515/znc-2023-0185

Abstract

Aspergillosis is one of the most common fungal infections that can threaten individuals with immune compromised condition. Due to the increasing resistance of pathogens to the existing antifungal drugs, it is difficult to tackle such disease conditions. Whereas, nikkomycin is an emerging safe and effective antifungal drug which causes fungal cell wall disruption by inhibiting chitin synthase. Hence, the study aims at the development of nikkomycin loaded PEG coated PLGA nanoparticles for its increased antifungal efficiency and inhibiting Aspergillus infections. The P-PLGA-Nik NPs were synthesized by w/o/w double emulsification method which resulted in a particle size of 208.3 ± 15 nm with a drug loading of 52.97 %. The NPs showed first order diffusion-controlled drug release which was sustained for 24 h. These nanoparticle’s antifungal efficacy was tested using the CLSI – M61 guidelines and the MIC₅₀ defined against Aspergillus flavus and Aspergillus fumigatus was found to be >32 μg/ml which was similar to the nikkomycin MIC. The hyphal tip bursting showed the fungal cell wall disruption. The non-cytotoxic and non-haemolytic nature highlights the drug safety profile.

Keywords: PEG; PLGA; nanoparticles; nikkomycin; chitin synthase; aspergillosis

Corresponding author: Vandana Ghormade, Nanobioscience Group, Agharkar Research Institute, GG Agarkar Road, Pune 411004, Maharashtra, India, E-mail: vandanaghormade@aripune.org

Funding source: Indian Council for Medical Research

Award Identifier / Grant number: ICMR Grant no5/8-4/20/Env/2020-NCD-II)

Acknowledgements

VG is grateful to the Indian Council of Medical Research (ICMR Grant no5/8-4/20/Env/2020-NCD-II) for providing the project grant and fellowship to KM.

Research ethics: Not applicable.
Author contributions: The authors has accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: All other authors state no conflict of interest.
Research funding: Indian Council of Medical Research Grant no5/8-4/20/Env/2020-NCD-II, Government of India.
Data availability: The raw data can be obtained on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/znc-2023-0185).

Received: 2023-12-31

Accepted: 2024-05-23

Published Online: 2024-06-07

Published in Print: 2024-05-27

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Supplementary Material