Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy
The inhaled delivery of lactic acid bacteria (LAB) probiotics has been demonstrated to exert therapeutic benefits to the lungs due to LAB's immunomodulatory activities. The development of inhaled probiotics formulation, however, is in its nascent stage limited to nebulized LAB. We developed a d...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/180524 |
| _version_ | 1826110328058937344 |
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| author | Tran, The-Thien Cheow, Wean Sin Pu, Siyu Park, Jin-Won Hadinoto, Kunn |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Tran, The-Thien Cheow, Wean Sin Pu, Siyu Park, Jin-Won Hadinoto, Kunn |
| author_sort | Tran, The-Thien |
| collection | NTU |
| description | The inhaled delivery of lactic acid bacteria (LAB) probiotics has been demonstrated to exert therapeutic benefits to the lungs due to LAB's immunomodulatory activities. The development of inhaled probiotics formulation, however, is in its nascent stage limited to nebulized LAB. We developed a dry powder inhaler (DPI) formulation of lactobacillus rhamnosus GG (LGG) intended for bronchiectasis maintenance therapy by spray freeze drying (SFD). The optimal DPI formulation (i.e., LGG: mannitol: lactose: leucine = 35: 45: 15: 5 wt.%) was determined based on the aerosolization efficiency (86% emitted dose and 26% respirable fraction) and LGG cell viability post-SFD (7 log CFU/mL per mg powder). The optimal DPI formulation was evaluated and compared to lyophilized naked LGG by its (1) adhesion capacity and cytotoxicity to human lung epithelium cells (i.e., A549 and 16HBE14o- cells) as well as its (2) effectiveness in inhibiting the growth and adhesion of Pseudomonas aeruginosa to lung cells. The optimal DPI of LGG exhibited similar non-cytotoxicity and adhesion capacity to lung cells to naked LGG. The DPI of LGG also inhibited the growth and adhesion of P. aeruginosa to the lung cells as effectively as the naked LGG. The present work established the feasibility of delivering the LAB probiotic by the DPI platform without adversely affecting LGG's anti-pseudomonal activities. |
| first_indexed | 2025-03-09T10:01:58Z |
| format | Journal Article |
| id | ntu-10356/180524 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-03-09T10:01:58Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1805242024-10-11T15:31:45Z Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy Tran, The-Thien Cheow, Wean Sin Pu, Siyu Park, Jin-Won Hadinoto, Kunn School of Chemistry, Chemical Engineering and Biotechnology Engineering Dry powder inhaler Pulmonary drug delivery The inhaled delivery of lactic acid bacteria (LAB) probiotics has been demonstrated to exert therapeutic benefits to the lungs due to LAB's immunomodulatory activities. The development of inhaled probiotics formulation, however, is in its nascent stage limited to nebulized LAB. We developed a dry powder inhaler (DPI) formulation of lactobacillus rhamnosus GG (LGG) intended for bronchiectasis maintenance therapy by spray freeze drying (SFD). The optimal DPI formulation (i.e., LGG: mannitol: lactose: leucine = 35: 45: 15: 5 wt.%) was determined based on the aerosolization efficiency (86% emitted dose and 26% respirable fraction) and LGG cell viability post-SFD (7 log CFU/mL per mg powder). The optimal DPI formulation was evaluated and compared to lyophilized naked LGG by its (1) adhesion capacity and cytotoxicity to human lung epithelium cells (i.e., A549 and 16HBE14o- cells) as well as its (2) effectiveness in inhibiting the growth and adhesion of Pseudomonas aeruginosa to lung cells. The optimal DPI of LGG exhibited similar non-cytotoxicity and adhesion capacity to lung cells to naked LGG. The DPI of LGG also inhibited the growth and adhesion of P. aeruginosa to the lung cells as effectively as the naked LGG. The present work established the feasibility of delivering the LAB probiotic by the DPI platform without adversely affecting LGG's anti-pseudomonal activities. Nanyang Technological University Published version This research was funded by School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University Singapore. 2024-10-10T02:14:42Z 2024-10-10T02:14:42Z 2024 Journal Article Tran, T., Cheow, W. S., Pu, S., Park, J. & Hadinoto, K. (2024). Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy. Pharmaceutics, 16(8), 980-. https://dx.doi.org/10.3390/pharmaceutics16080980 1999-4923 https://hdl.handle.net/10356/180524 10.3390/pharmaceutics16080980 39204326 2-s2.0-85202528108 8 16 980 en Pharmaceutics © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). application/pdf |
| spellingShingle | Engineering Dry powder inhaler Pulmonary drug delivery Tran, The-Thien Cheow, Wean Sin Pu, Siyu Park, Jin-Won Hadinoto, Kunn Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy |
| title | Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy |
| title_full | Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy |
| title_fullStr | Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy |
| title_full_unstemmed | Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy |
| title_short | Dry powder inhaler formulation of Lactobacillus rhamnosus GG targeting Pseudomonas aeruginosa infection in bronchiectasis maintenance therapy |
| title_sort | dry powder inhaler formulation of lactobacillus rhamnosus gg targeting pseudomonas aeruginosa infection in bronchiectasis maintenance therapy |
| topic | Engineering Dry powder inhaler Pulmonary drug delivery |
| url | https://hdl.handle.net/10356/180524 |
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