A novel fungal-targeted drug delivery system dectin-1-targeted-PEG-amino acid polymer block enhances antifungal activity and reduces cytotoxicity of amphotericin B
We investigated whether the cytotoxicity of the antifungal drug amphotericin B (AmB) could be mitigated using Dectin-1 (DEC)-installed-polymeric micelles based on poly(ethylene glycol) (PEG)-amino acid block copolymers. In this study, DEC-installed micelles formed by carboxydimethylmaleic anhydride-...
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| Published in | Journal of drug delivery science and technology Vol. 100; p. 106073 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
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Elsevier B.V
01.10.2024
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| Abstract | We investigated whether the cytotoxicity of the antifungal drug amphotericin B (AmB) could be mitigated using Dectin-1 (DEC)-installed-polymeric micelles based on poly(ethylene glycol) (PEG)-amino acid block copolymers. In this study, DEC-installed micelles formed by carboxydimethylmaleic anhydride-modified PEG-poly(L-lysine) (PEG-pLL(CDM)) or PEG-poly(β-benzyl-L-aspartate) (PEG-pBLA) were prepared and compared with uninstalled DEC-micelles. The polymeric micelles confirmed the acquisition of accumulation on fungi by installing DEC. DEC-micelles loaded with AmB (DEC-AmB/m) showed higher antifungal activity in vitro than AmB/m. The administration of DEC-AmB/m with 20 μg/mL of AmB to cultured cells inhibited the release of intracellular lactate dehydrogenase. In the evaluation of treatment efficacy using an Aspergillus-infected silkworm model, DEC-AmB/m at 5 μg/larva (amphotericin B equivalent) improved silkworm survival compared with AmB 5 μg/larva treatment. These results suggest that drug-loaded micelles may improve the clinical efficacy and safety of AmB and highlight the potential of DEC-PEG-poly(amino acids) modification for compound delivery against fungal infections.
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| AbstractList | We investigated whether the cytotoxicity of the antifungal drug amphotericin B (AmB) could be mitigated using Dectin-1 (DEC)-installed-polymeric micelles based on poly(ethylene glycol) (PEG)-amino acid block copolymers. In this study, DEC-installed micelles formed by carboxydimethylmaleic anhydride-modified PEG-poly(L-lysine) (PEG-pLL(CDM)) or PEG-poly(β-benzyl-L-aspartate) (PEG-pBLA) were prepared and compared with uninstalled DEC-micelles. The polymeric micelles confirmed the acquisition of accumulation on fungi by installing DEC. DEC-micelles loaded with AmB (DEC-AmB/m) showed higher antifungal activity in vitro than AmB/m. The administration of DEC-AmB/m with 20 μg/mL of AmB to cultured cells inhibited the release of intracellular lactate dehydrogenase. In the evaluation of treatment efficacy using an Aspergillus-infected silkworm model, DEC-AmB/m at 5 μg/larva (amphotericin B equivalent) improved silkworm survival compared with AmB 5 μg/larva treatment. These results suggest that drug-loaded micelles may improve the clinical efficacy and safety of AmB and highlight the potential of DEC-PEG-poly(amino acids) modification for compound delivery against fungal infections.
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| ArticleNumber | 106073 |
| Author | Inukai, Tatsuya Chen, Pengwen Kokuba, Hiroko Cabral, Horacio Nakamura, Shigeki |
| Author_xml | – sequence: 1 givenname: Tatsuya surname: Inukai fullname: Inukai, Tatsuya organization: Department of Microbiology, Tokyo Medical University, Tokyo, Japan – sequence: 2 givenname: Pengwen orcidid: 0000-0002-5663-2192 surname: Chen fullname: Chen, Pengwen organization: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan – sequence: 3 givenname: Hiroko surname: Kokuba fullname: Kokuba, Hiroko organization: Laboratory of Electron Microscopy, Tokyo Medical University, Tokyo, Japan – sequence: 4 givenname: Horacio surname: Cabral fullname: Cabral, Horacio organization: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan – sequence: 5 givenname: Shigeki orcidid: 0000-0001-5272-8886 surname: Nakamura fullname: Nakamura, Shigeki email: shigenak@tokyo-med.ac.jp organization: Department of Microbiology, Tokyo Medical University, Tokyo, Japan |
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| Keywords | Amphotericin B Aspergillus fumigatus Drug delivery system |
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| SubjectTerms | Amphotericin B Aspergillus fumigatus Drug delivery system |
| Title | A novel fungal-targeted drug delivery system dectin-1-targeted-PEG-amino acid polymer block enhances antifungal activity and reduces cytotoxicity of amphotericin B |
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