Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC<sup>®</sup> Natural Adjuvant against Aspergillosis
Invasive pulmonary aspergillosis represents one of the most serious fungal infections among immunocompromised patients. In this study, we aimed to analyze the in vivo efficacy of prophylactic oral amphotericin B (AMB) encapsulated in modified chitosan-nanoparticles (Nanomerics’ Molecular E...
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| Format: | Article |
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MDPI AG
2019-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/9/456 |
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| author | Alba Pérez-Cantero Dolores R. Serrano Patricia Navarro-Rodríguez Andreas G. Schätzlein Ijeoma F. Uchegbu Juan J. Torrado Javier Capilla |
| author_facet | Alba Pérez-Cantero Dolores R. Serrano Patricia Navarro-Rodríguez Andreas G. Schätzlein Ijeoma F. Uchegbu Juan J. Torrado Javier Capilla |
| author_sort | Alba Pérez-Cantero |
| collection | DOAJ |
| description | Invasive pulmonary aspergillosis represents one of the most serious fungal infections among immunocompromised patients. In this study, we aimed to analyze the in vivo efficacy of prophylactic oral amphotericin B (AMB) encapsulated in modified chitosan-nanoparticles (Nanomerics’ Molecular Envelope Technology (MET)) supplemented with a standardized extract of cultured <i>Lentinula edodes</i> mycelia (AHCC<sup>®</sup>) in a murine model of pulmonary aspergillosis. We determined fungal burden and survival of mice and additionally, we carried out a cytokine analysis in an attempt to understand the immunomodulation of the extract. Our results evidenced equivalent efficacy between orally administered AMB-MET and the intravenous liposomal AMB marketed formulation. Addition of the AHCC<sup>®</sup> supplement significantly improved efficacy in terms of burden reduction and survival increase of both oral and intravenous AMB therapies compared to the untreated control group. Moreover, a protective effect of the extract was observed in terms of weight loss. Regarding the cytokine profiles, the Th1 immune response was stimulated in treated animals when compared to the control group. This response was marked by an enhancement in the MCP-1, GM-CSF, VEGF, RANTES and IL-17 levels and a decrease in the IL-6, a biomarker related to the severity of the infection. |
| first_indexed | 2024-04-14T05:20:02Z |
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| id | doaj.art-f3dc69a3578d4fc6aa457f09b63791a7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T05:20:02Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-f3dc69a3578d4fc6aa457f09b63791a72022-12-22T02:10:15ZengMDPI AGPharmaceutics1999-49232019-09-0111945610.3390/pharmaceutics11090456pharmaceutics11090456Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC<sup>®</sup> Natural Adjuvant against AspergillosisAlba Pérez-Cantero0Dolores R. Serrano1Patricia Navarro-Rodríguez2Andreas G. Schätzlein3Ijeoma F. Uchegbu4Juan J. Torrado5Javier Capilla6Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili and Institut d’Investigació Sanitària Pere Virgili (IISPV), 43201 Reus, Tarragona, SpainDepartament of Pharmaceutics and Food Technology and Instituto Universitario de Farmacia Industrial (IUFI), School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, SpainUnitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili and Institut d’Investigació Sanitària Pere Virgili (IISPV), 43201 Reus, Tarragona, SpainNanomerics Ltd., St. Albans AL1 1SR, UKUCL School of Pharmacy, 29–39, Brunswick Square, London WC1N 1AX, UKDepartament of Pharmaceutics and Food Technology and Instituto Universitario de Farmacia Industrial (IUFI), School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, SpainUnitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili and Institut d’Investigació Sanitària Pere Virgili (IISPV), 43201 Reus, Tarragona, SpainInvasive pulmonary aspergillosis represents one of the most serious fungal infections among immunocompromised patients. In this study, we aimed to analyze the in vivo efficacy of prophylactic oral amphotericin B (AMB) encapsulated in modified chitosan-nanoparticles (Nanomerics’ Molecular Envelope Technology (MET)) supplemented with a standardized extract of cultured <i>Lentinula edodes</i> mycelia (AHCC<sup>®</sup>) in a murine model of pulmonary aspergillosis. We determined fungal burden and survival of mice and additionally, we carried out a cytokine analysis in an attempt to understand the immunomodulation of the extract. Our results evidenced equivalent efficacy between orally administered AMB-MET and the intravenous liposomal AMB marketed formulation. Addition of the AHCC<sup>®</sup> supplement significantly improved efficacy in terms of burden reduction and survival increase of both oral and intravenous AMB therapies compared to the untreated control group. Moreover, a protective effect of the extract was observed in terms of weight loss. Regarding the cytokine profiles, the Th1 immune response was stimulated in treated animals when compared to the control group. This response was marked by an enhancement in the MCP-1, GM-CSF, VEGF, RANTES and IL-17 levels and a decrease in the IL-6, a biomarker related to the severity of the infection.https://www.mdpi.com/1999-4923/11/9/456aspergillosisamphotericin Boral deliverychitosanshiitake<i>Lentinula edodes</i>AHCC<sup>®</sup>Molecular Envelope Technology |
| spellingShingle | Alba Pérez-Cantero Dolores R. Serrano Patricia Navarro-Rodríguez Andreas G. Schätzlein Ijeoma F. Uchegbu Juan J. Torrado Javier Capilla Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC<sup>®</sup> Natural Adjuvant against Aspergillosis Pharmaceutics aspergillosis amphotericin B oral delivery chitosan shiitake <i>Lentinula edodes</i> AHCC<sup>®</sup> Molecular Envelope Technology |
| title | Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC<sup>®</sup> Natural Adjuvant against Aspergillosis |
| title_full | Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC<sup>®</sup> Natural Adjuvant against Aspergillosis |
| title_fullStr | Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC<sup>®</sup> Natural Adjuvant against Aspergillosis |
| title_full_unstemmed | Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC<sup>®</sup> Natural Adjuvant against Aspergillosis |
| title_short | Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC<sup>®</sup> Natural Adjuvant against Aspergillosis |
| title_sort | increased efficacy of oral fixed dose combination of amphotericin b and ahcc sup r sup natural adjuvant against aspergillosis |
| topic | aspergillosis amphotericin B oral delivery chitosan shiitake <i>Lentinula edodes</i> AHCC<sup>®</sup> Molecular Envelope Technology |
| url | https://www.mdpi.com/1999-4923/11/9/456 |
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