Ma, Cheng;
Chow, Michael YT;
Zhang, Chengyang;
Goldbaum, Paulina;
Hsieh, Jamie Chien-Ming;
Lam, Jenny KW;
(2025)
Robust peptide/RNA complexes prepared with microfluidic mixing for pulmonary delivery by nebulisation.
Drug Delivery and Translational Research
10.1007/s13346-024-01773-w.
(In press).
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Abstract
Small interfering RNA (siRNA) and messenger RNA (mRNA) have drawn considerable attention in recent years due to their ability to modulate the expression of specific disease-related proteins. However, it is difficult to find safe, robust, and effective RNA delivery systems suitable for pulmonary delivery to treat lung diseases. In this study, two cationic peptides, namely LAH4-L1 and PEG12KL4, were employed as non-viral vectors for siRNA and mRNA delivery. Four formulations (i.e. LAH4-L1/siRNA; PEG12KL4/siRNA; LAH4-L1/mRNA and PEG12KL4/mRNA) were investigated. Microfluidic mixing method was utilised to fabricate RNA complexes in a controllable and reproducible manner. Upon optimisation of the microfluidic mixing protocol, a vibrating mesh nebuliser was employed to aerosolise the RNA complexes, and their transfection efficiency was evaluated on A549 and BEAS-2B cells. Following nebulisation, inhalable mist was generated for all RNA formulations with mass median aerodynamic diameter below 5 μm. Although the hydrodynamic particle sizes of the RNA complexes were significantly reduced to around 100 nm after nebulisation regardless of the original size of the complexes prior to nebulisation, the RNA binding efficiency and the in vitro RNA transfection ability of all the peptide formulations were successfully preserved with no significant differences compared to the same system before nebulisation. The current result indicates that both LAH4-L1 and PEG12KL4 hold significant potential for future clinical application for pulmonary siRNA and mRNA delivery through nebulisation.
| Type: | Article |
|---|---|
| Title: | Robust peptide/RNA complexes prepared with microfluidic mixing for pulmonary delivery by nebulisation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s13346-024-01773-w |
| Publisher version: | https://doi.org/10.1007/s13346-024-01773-w |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Aerosolisation, Inhalation, mRNA, siRNA, Transfection, Vibrating mesh nebuliser |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10205433 |
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