Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy
Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of s...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/12/2044 |
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| author | Zitong Shao Waiting Tai Yingshan Qiu Rico C. H. Man Qiuying Liao Michael Y. T. Chow Philip C. L. Kwok Jenny K. W. Lam |
| author_facet | Zitong Shao Waiting Tai Yingshan Qiu Rico C. H. Man Qiuying Liao Michael Y. T. Chow Philip C. L. Kwok Jenny K. W. Lam |
| author_sort | Zitong Shao |
| collection | DOAJ |
| description | Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (<i>w</i>/<i>w</i>) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma. |
| first_indexed | 2024-03-10T03:20:31Z |
| format | Article |
| id | doaj.art-7acc961ce28e4a4096146d3d5c9bb907 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:20:31Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7acc961ce28e4a4096146d3d5c9bb9072023-11-23T10:05:09ZengMDPI AGPharmaceutics1999-49232021-11-011312204410.3390/pharmaceutics13122044Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis TherapyZitong Shao0Waiting Tai1Yingshan Qiu2Rico C. H. Man3Qiuying Liao4Michael Y. T. Chow5Philip C. L. Kwok6Jenny K. W. Lam7Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, ChinaAdvanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, ChinaDepartment of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, ChinaDepartment of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, ChinaAdvanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, AustraliaAdvanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, ChinaMulti-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (<i>w</i>/<i>w</i>) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.https://www.mdpi.com/1999-4923/13/12/2044capreomycindry powder aerosolinhalationpulmonary deliveryspray dryingtuberculosis |
| spellingShingle | Zitong Shao Waiting Tai Yingshan Qiu Rico C. H. Man Qiuying Liao Michael Y. T. Chow Philip C. L. Kwok Jenny K. W. Lam Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy Pharmaceutics capreomycin dry powder aerosol inhalation pulmonary delivery spray drying tuberculosis |
| title | Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy |
| title_full | Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy |
| title_fullStr | Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy |
| title_full_unstemmed | Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy |
| title_short | Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy |
| title_sort | spray dried powder formulation of capreomycin designed for inhaled tuberculosis therapy |
| topic | capreomycin dry powder aerosol inhalation pulmonary delivery spray drying tuberculosis |
| url | https://www.mdpi.com/1999-4923/13/12/2044 |
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