Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy
Antibiotic-polyelectrolyte nanoparticle complex (or nanoplex in short) has been recently demonstrated as a superior antibiotic delivery system to the native antibiotic in bronchiectasis therapy owed to its ability to overcome the lung's mucus barrier and generate high localized antibiotic expos...
| Main Authors: | , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Online Access: | https://hdl.handle.net/10356/161082 |
| _version_ | 1811689801261252608 |
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| author | Tran, The-Thien Hadinoto, Kunn |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Tran, The-Thien Hadinoto, Kunn |
| author_sort | Tran, The-Thien |
| collection | NTU |
| description | Antibiotic-polyelectrolyte nanoparticle complex (or nanoplex in short) has been recently demonstrated as a superior antibiotic delivery system to the native antibiotic in bronchiectasis therapy owed to its ability to overcome the lung's mucus barrier and generate high localized antibiotic exposure in the infected sites. The present work aimed to further improve the mucus permeability, hence the antibacterial efficacy of the nanoplex, by incorporating mucolytic enzyme papain (PAP) at the nanoplex formation step to produce PAP-decorated antibiotic-polyelectrolyte nanoplex exhibiting built-in mucolytic capability. Ciprofloxacin (CIP) and dextran sulfate (DXT) were used as the models for antibiotics and polyelectrolyte, respectively. The results showed that the PAP inclusion had minimal effects on the physical characteristics, preparation efficiency, and dissolution of the CIP-DXT nanoplex. The optimal CIP-(DXT-PAP) nanoplex exhibited size and zeta potential of approximately 200 nm and -50 mV with CIP and PAP payloads of 60% and 32% (w/w), respectively. The nanoplex was prepared at high efficiency with larger than 80% CIP and PAP utilization rates. The CIP-(DXT-PAP) nanoplex exhibited tenfold improvement in the mucus permeability compared to its CIP-DXT nanoplex counterpart, resulting in the former's superior bactericidal activity against clinical Pseudomonas aeruginosa biofilm in the presence of mucus barrier. A trade-off, nevertheless, existed between antibacterial efficacy and cytotoxicity towards human lung epithelium cells upon the incorporation of PAP above a certain concentration threshold. Therefore, the optimal dosing of the CIP-(DXT-PAP) nanoplex must be carefully determined. |
| first_indexed | 2024-10-01T05:53:52Z |
| format | Journal Article |
| id | ntu-10356/161082 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:53:52Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1610822022-08-15T04:09:21Z Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy Tran, The-Thien Hadinoto, Kunn School of Chemical and Biomedical Engineering Engineering::Bioengineering Drug–Polyelectrolyte Complex Antibiotic Antibiotic-polyelectrolyte nanoparticle complex (or nanoplex in short) has been recently demonstrated as a superior antibiotic delivery system to the native antibiotic in bronchiectasis therapy owed to its ability to overcome the lung's mucus barrier and generate high localized antibiotic exposure in the infected sites. The present work aimed to further improve the mucus permeability, hence the antibacterial efficacy of the nanoplex, by incorporating mucolytic enzyme papain (PAP) at the nanoplex formation step to produce PAP-decorated antibiotic-polyelectrolyte nanoplex exhibiting built-in mucolytic capability. Ciprofloxacin (CIP) and dextran sulfate (DXT) were used as the models for antibiotics and polyelectrolyte, respectively. The results showed that the PAP inclusion had minimal effects on the physical characteristics, preparation efficiency, and dissolution of the CIP-DXT nanoplex. The optimal CIP-(DXT-PAP) nanoplex exhibited size and zeta potential of approximately 200 nm and -50 mV with CIP and PAP payloads of 60% and 32% (w/w), respectively. The nanoplex was prepared at high efficiency with larger than 80% CIP and PAP utilization rates. The CIP-(DXT-PAP) nanoplex exhibited tenfold improvement in the mucus permeability compared to its CIP-DXT nanoplex counterpart, resulting in the former's superior bactericidal activity against clinical Pseudomonas aeruginosa biofilm in the presence of mucus barrier. A trade-off, nevertheless, existed between antibacterial efficacy and cytotoxicity towards human lung epithelium cells upon the incorporation of PAP above a certain concentration threshold. Therefore, the optimal dosing of the CIP-(DXT-PAP) nanoplex must be carefully determined. Nanyang Technological University This work was supported by LKCMedicine-SCBE Collaborative Grant (CG-04/16) from Nanyang Technological University Singapore. 2022-08-15T04:09:20Z 2022-08-15T04:09:20Z 2020 Journal Article Tran, T. & Hadinoto, K. (2020). Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy. Colloids and Surfaces. B, Biointerfaces, 193, 111095-. https://dx.doi.org/10.1016/j.colsurfb.2020.111095 0927-7765 https://hdl.handle.net/10356/161082 10.1016/j.colsurfb.2020.111095 32416520 2-s2.0-85084464042 193 111095 en CG-04/16 Colloids and surfaces. B, Biointerfaces © 2020 Elsevier B.V. All rights reserved. |
| spellingShingle | Engineering::Bioengineering Drug–Polyelectrolyte Complex Antibiotic Tran, The-Thien Hadinoto, Kunn Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy |
| title | Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy |
| title_full | Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy |
| title_fullStr | Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy |
| title_full_unstemmed | Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy |
| title_short | Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy |
| title_sort | ternary nanoparticle complex of antibiotic polyelectrolyte and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy |
| topic | Engineering::Bioengineering Drug–Polyelectrolyte Complex Antibiotic |
| url | https://hdl.handle.net/10356/161082 |
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