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Open AccessArticle

Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections

1
Food and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy
2
Interdipartmental Center for Innovation in Health Products, BIOPHARMANET TEC, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy
3
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, 1349-008 Lisbon, Portugal
*
Author to whom correspondence should be addressed.
Present address: Aptuit Srl, Via Alessandro Fleming, 4, Verona, Italy.
Pharmaceutics 2019, 11(5), 203; https://doi.org/10.3390/pharmaceutics11050203
Received: 13 March 2019 / Revised: 19 April 2019 / Accepted: 21 April 2019 / Published: 1 May 2019
(This article belongs to the Special Issue Advances in Pulmonary Drug Delivery)
Tuberculosis resistant cases have been estimated to grow every year. Besides Mycobacterium tuberculosis, 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. View Full-Text
Keywords: nanoparticles; dry powder inhaler; sodium hyaluronate; mycobacteria; antibiotics; efflux pump inhibitor nanoparticles; dry powder inhaler; sodium hyaluronate; mycobacteria; antibiotics; efflux pump inhibitor
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Rossi, I.; Buttini, F.; Sonvico, F.; Affaticati, F.; Martinelli, F.; Annunziato, G.; Machado, D.; Viveiros, M.; Pieroni, M.; Bettini, R. Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections. Pharmaceutics 2019, 11, 203.

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