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Aerosol-mediated non-viral lung gene therapy: The potential of aminoglycoside-based cationic liposomes
- Source :
- Pharmaceutics, Pharmaceutics, 2022, 14 (1), pp.25. ⟨10.3390/pharmaceutics14010025⟩, Pharmaceutics, MDPI, 2022, 14 (1), pp.25. ⟨10.3390/pharmaceutics14010025⟩, Pharmaceutics; Volume 14; Issue 1; Pages: 25, Pharmaceutics, Vol 14, Iss 25, p 25 (2022)
- Publication Year :
- 2022
- Publisher :
- MDPI, 2022.
-
Abstract
- International audience; Aerosol lung gene therapy using non-viral delivery systems represents a credible therapeutic strategy for chronic respiratory diseases, such as cystic fibrosis (CF). Progress in CF clinical setting using the lipidic formulation GL67A has demonstrated the relevance of such a strategy while emphasizing the need for more potent gene transfer agents. In recent years, many novel non-viral gene delivery vehicles were proposed as potential alternatives to GL67 cationic lipid. However, they were usually evaluated using procedures difficult or even impossible to implement in clinical practice. In this study, a clinically-relevant administration protocol via aerosol in murine lungs was used to conduct a comparative study with GL67A. Diverse lipidic compounds were used to prepare a series of formulations inspired by the composition of GL67A. While some of these formulations were ineffective at transfecting murine lungs, others demonstrated modest-to-very-efficient activities and a series of structure-activity relationships were unveiled. Lipidic aminoglycoside derivative-based formulations were found to be at least as efficient as GL67A following aerosol delivery of a luciferase-encoding plasmid DNA. A single aerosol treatment with one such formulation was found to mediate long-term lung transgene expression, exceeding half the animal’s lifetime. This study clearly supports the potential of aminoglycoside-based cationic lipids as potent GL67-alternative scaffolds for further enhanced aerosol non-viral lung gene therapy for diseases such as CF. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Subjects :
- Aminoglycoside-based cationic lipids
0303 health sciences
Structure-activity
Pharmaceutical Science
respiratory system
Article
Cystic fibrosis
Lipidic formulations
3. Good health
RS1-441
Lung gene therapy
Nebulization
03 medical and health sciences
Pharmacy and materia medica
aminoglycoside-based cationic lipids
cystic fibrosis
lipidic formulations
lung gene therapy
nebulization
structure-activity
0302 clinical medicine
030220 oncology & carcinogenesis
[CHIM] Chemical Sciences
[CHIM]Chemical Sciences
030304 developmental biology
Subjects
Details
- Language :
- English
- ISSN :
- 19994923
- Database :
- OpenAIRE
- Journal :
- Pharmaceutics, Pharmaceutics, 2022, 14 (1), pp.25. ⟨10.3390/pharmaceutics14010025⟩, Pharmaceutics, MDPI, 2022, 14 (1), pp.25. ⟨10.3390/pharmaceutics14010025⟩, Pharmaceutics; Volume 14; Issue 1; Pages: 25, Pharmaceutics, Vol 14, Iss 25, p 25 (2022)
- Accession number :
- edsair.doi.dedup.....f941ce132c74d485538cfee06cf2cafc