Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections
Tuberculosis resistant cases have been estimated to grow every year. Besides <i>Mycobacterium tuberculosis</i>, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/5/203 |
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| author | Irene Rossi Francesca Buttini Fabio Sonvico Filippo Affaticati Francesco Martinelli Giannamaria Annunziato Diana Machado Miguel Viveiros Marco Pieroni Ruggero Bettini |
| author_facet | Irene Rossi Francesca Buttini Fabio Sonvico Filippo Affaticati Francesco Martinelli Giannamaria Annunziato Diana Machado Miguel Viveiros Marco Pieroni Ruggero Bettini |
| author_sort | Irene Rossi |
| collection | DOAJ |
| description | Tuberculosis resistant cases have been estimated to grow every year. Besides <i>Mycobacterium tuberculosis</i>, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections an inhalable antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight sodium hyaluronate sub-micron particles were efficiently loaded with rifampicin, isoniazid and verapamil, and transformed in highly respirable microparticles (mean volume diameter: 1 μm) by spray drying. These particles were able to regenerate their original size upon contact with aqueous environment with mechanical stirring or sonication. The in vitro drugs release profile from the powder was characterized by a slow release rate, favorable to maintain a high drug level inside AMs. In vitro antimicrobial activity and ex vivo macrophage infection assays employing susceptible and drug resistant strains were carried out. No significant differences were observed when the powder, which did not compromise the AMs viability after a five-day exposure, was compared to the same formulation without verapamil. However, both preparations achieved more than 80% reduction in bacterial viability irrespective of the drug resistance profile. This approach can be considered appropriate to treat mycobacterial respiratory infections, regardless the level of drug resistance. |
| first_indexed | 2024-04-11T13:03:50Z |
| format | Article |
| id | doaj.art-7e5697530911499bbbb14697cb0a4679 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T13:03:50Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7e5697530911499bbbb14697cb0a46792022-12-22T04:22:51ZengMDPI AGPharmaceutics1999-49232019-05-0111520310.3390/pharmaceutics11050203pharmaceutics11050203Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary InfectionsIrene Rossi0Francesca Buttini1Fabio Sonvico2Filippo Affaticati3Francesco Martinelli4Giannamaria Annunziato5Diana Machado6Miguel Viveiros7Marco Pieroni8Ruggero Bettini9Food and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyGlobal Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, 1349-008 Lisbon, PortugalGlobal Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, 1349-008 Lisbon, PortugalFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyTuberculosis resistant cases have been estimated to grow every year. Besides <i>Mycobacterium tuberculosis</i>, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections an inhalable antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight sodium hyaluronate sub-micron particles were efficiently loaded with rifampicin, isoniazid and verapamil, and transformed in highly respirable microparticles (mean volume diameter: 1 μm) by spray drying. These particles were able to regenerate their original size upon contact with aqueous environment with mechanical stirring or sonication. The in vitro drugs release profile from the powder was characterized by a slow release rate, favorable to maintain a high drug level inside AMs. In vitro antimicrobial activity and ex vivo macrophage infection assays employing susceptible and drug resistant strains were carried out. No significant differences were observed when the powder, which did not compromise the AMs viability after a five-day exposure, was compared to the same formulation without verapamil. However, both preparations achieved more than 80% reduction in bacterial viability irrespective of the drug resistance profile. This approach can be considered appropriate to treat mycobacterial respiratory infections, regardless the level of drug resistance.https://www.mdpi.com/1999-4923/11/5/203nanoparticlesdry powder inhalersodium hyaluronatemycobacteriaantibioticsefflux pump inhibitor |
| spellingShingle | Irene Rossi Francesca Buttini Fabio Sonvico Filippo Affaticati Francesco Martinelli Giannamaria Annunziato Diana Machado Miguel Viveiros Marco Pieroni Ruggero Bettini Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections Pharmaceutics nanoparticles dry powder inhaler sodium hyaluronate mycobacteria antibiotics efflux pump inhibitor |
| title | Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections |
| title_full | Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections |
| title_fullStr | Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections |
| title_full_unstemmed | Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections |
| title_short | Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections |
| title_sort | sodium hyaluronate nanocomposite respirable microparticles to tackle antibiotic resistance with potential application in treatment of mycobacterial pulmonary infections |
| topic | nanoparticles dry powder inhaler sodium hyaluronate mycobacteria antibiotics efflux pump inhibitor |
| url | https://www.mdpi.com/1999-4923/11/5/203 |
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