Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics
Nanoparticles exhibit potential as drug carriers in biomedicine due to their high surface-to-volume ratio that allows for facile drug loading. Nanosized drug delivery systems have been proposed for the delivery of biologics facilitating their transport across epithelial layers and maintaining their...
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sg-ntu-dr.10356-1449452023-03-05T16:47:22Z Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics Tsikourkitoudi, Vasiliki Karlsson, Jens Merkl, Padryk Loh, Edmund Henriques-Normark, Birgitta Sotiriou, Georgios A. Lee Kong Chian School of Medicine (LKCMedicine) Singapore Centre for Environmental Life Sciences and Engineering (SCELSE) Science::Medicine Nanocarriers Drug Delivery Nanoparticles exhibit potential as drug carriers in biomedicine due to their high surface-to-volume ratio that allows for facile drug loading. Nanosized drug delivery systems have been proposed for the delivery of biologics facilitating their transport across epithelial layers and maintaining their stability against proteolytic degradation. Here, we capitalize on a nanomanufacturing process famous for its scalability and reproducibility, flame spray pyrolysis, and produce calcium phosphate (CaP) nanoparticles with tailored properties. The as-prepared nanoparticles are loaded with bovine serum albumin (model protein) and bradykinin (model peptide) by physisorption and the physicochemical parameters influencing their loading capacity are investigated. Furthermore, we implement the developed protocol by formulating CaP nanoparticles loaded with the LL-37 antimicrobial peptide, which is a biological drug currently involved in clinical trials. High loading values along with high reproducibility are achieved. Moreover, it is shown that CaP nanoparticles protect LL-37 from proteolysis in vitro. We also demonstrate that LL-37 retains its antimicrobial activity against Escherichia coli and Streptococcus pneumoniae when loaded on nanoparticles in vitro. Therefore, we highlight the potential of nanocarriers for optimization of the therapeutic profile of existing and emerging biological drugs. Published version This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC Grant agreement n° 758705). Funding from the Karolinska Institutet Board of Research, the Swedish Research Council (2016-03471; 2016-00228; 2016-01861; 2018-05798), the Jeansson Foundations (JS2016-0029), the Torsten Söderberg Foundation (M87/18), the Swedish Foundation for Strategic Research (SSF), Stockholm County Council, and the Knut and Alice Wallenberg Foundation is kindly acknowledged. 2020-12-04T05:29:48Z 2020-12-04T05:29:48Z 2020 Journal Article Tsikourkitoudi, V., Karlsson, J., Merkl, P., Loh, E., Henriques-Normark, B., & Sotiriou, G. A. (2020). Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics. Molecules, 25(7), 1747-. doi:10.3390/molecules25071747 1420-3049 https://hdl.handle.net/10356/144945 10.3390/molecules25071747 32290273 7 25 en Molecules © 2020 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 (http://creativecommons.org/licenses/by/4.0/). application/pdf |
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Science::Medicine Nanocarriers Drug Delivery Tsikourkitoudi, Vasiliki Karlsson, Jens Merkl, Padryk Loh, Edmund Henriques-Normark, Birgitta Sotiriou, Georgios A. Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics |
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Nanoparticles exhibit potential as drug carriers in biomedicine due to their high surface-to-volume ratio that allows for facile drug loading. Nanosized drug delivery systems have been proposed for the delivery of biologics facilitating their transport across epithelial layers and maintaining their stability against proteolytic degradation. Here, we capitalize on a nanomanufacturing process famous for its scalability and reproducibility, flame spray pyrolysis, and produce calcium phosphate (CaP) nanoparticles with tailored properties. The as-prepared nanoparticles are loaded with bovine serum albumin (model protein) and bradykinin (model peptide) by physisorption and the physicochemical parameters influencing their loading capacity are investigated. Furthermore, we implement the developed protocol by formulating CaP nanoparticles loaded with the LL-37 antimicrobial peptide, which is a biological drug currently involved in clinical trials. High loading values along with high reproducibility are achieved. Moreover, it is shown that CaP nanoparticles protect LL-37 from proteolysis in vitro. We also demonstrate that LL-37 retains its antimicrobial activity against Escherichia coli and Streptococcus pneumoniae when loaded on nanoparticles in vitro. Therefore, we highlight the potential of nanocarriers for optimization of the therapeutic profile of existing and emerging biological drugs. |
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Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Tsikourkitoudi, Vasiliki Karlsson, Jens Merkl, Padryk Loh, Edmund Henriques-Normark, Birgitta Sotiriou, Georgios A. |
format |
Article |
author |
Tsikourkitoudi, Vasiliki Karlsson, Jens Merkl, Padryk Loh, Edmund Henriques-Normark, Birgitta Sotiriou, Georgios A. |
author_sort |
Tsikourkitoudi, Vasiliki |
title |
Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics |
title_short |
Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics |
title_full |
Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics |
title_fullStr |
Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics |
title_full_unstemmed |
Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics |
title_sort |
flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics |
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2020 |
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https://hdl.handle.net/10356/144945 |
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1759858048693698560 |