Scalable Production of Lipid Nanoparticles Containing Amphotericin B
Lipid-based formulations have been developed to improve stability profiles, tolerability, and toxicity profiles of small molecule drugs. However, manufacture of such formulations involving lipophilic compounds can be labor-intensive and difficult to scale because of solubility and solvent compatibil...
| Publié dans: | Langmuir : the ACS journal of surfaces and colloids. - 1985. - 37(2021), 24 vom: 22. Juni, Seite 7312-7319 |
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| Auteur principal: | |
| Autres auteurs: | , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2021
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| Accès à la collection: | Langmuir : the ACS journal of surfaces and colloids |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't Lipids RNA, Small Interfering Amphotericin B 7XU7A7DROE |
| Résumé: | Lipid-based formulations have been developed to improve stability profiles, tolerability, and toxicity profiles of small molecule drugs. However, manufacture of such formulations involving lipophilic compounds can be labor-intensive and difficult to scale because of solubility and solvent compatibility issues. We have developed a rapid and scalable approach using rapid-mixing techniques to generate homogeneous lipid nanoparticle (LNP) formulations of siRNA, triglycerides, and hydrophilic weak-base drugs. Here, we used this approach to entrap a hydrophobic small molecule, Amphotericin B (AmpB), a hydrophobic drug not soluble in ethanol. The three prototypes presented in this study were derived from LNP-siRNA systems, triglyceride nanoparticles, and liposomal systems. Cryogenic transmission electron microscopy (cryo-TEM) revealed that all three LNP-AmpB formulations retain structural characteristics of the parent (AmpB-free) LNPs, with particles remaining stable for at least 1 month. All formulations showed similar in vitro toxicity profiles in comparison to AmBisome. Importantly, the formulations have a 2.5-fold improved IC50 for fungal growth inhibition as compared to AmBisome in in vitro efficacy studies. These results demonstrate that the rapid-mixing technology combined with dimethyl sulfoxide (DMSO) for drugs insoluble in other organic solvents can be a powerful manufacturing method for the generation of stable LNP drug formulations |
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| Description: | Date Completed 28.06.2021 Date Revised 28.06.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/acs.langmuir.1c00530 |