Continuous-Flow Production of Perfluorocarbon-Loaded Polymeric Nanoparticles: From the Bench to Clinic
| Autor: | Edyta Swider, Olga Koshkina, Paul B. White, Christophe A. Serra, Esmee Hoogendijk, Ingo Lieberwirth, Mangala Srinivas, N. Koen van Riessen, Gunnar Glaßer, Anna Musyanovych, Alexander H. J. Staal |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2020 |
| Předmět: |
Biodistribution
Materials science genetic structures Surface Properties Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Sonication Microfluidics microfluidic microfluidics Nanoparticle 19F MRI multimodal imaging Synthetic Organic Chemistry 02 engineering and technology oxygen carriers 010402 general chemistry 01 natural sciences Theranostic Nanomedicine chemistry.chemical_compound Pulmonary surfactant Polylactic Acid-Polyglycolic Acid Copolymer Humans General Materials Science Particle Size Cells Cultured Fluorocarbons Aqueous solution Molecular Structure perfluorocarbon ultrasound Microfluidic Analytical Techniques 021001 nanoscience & nanotechnology Magnetic Resonance Imaging 0104 chemical sciences Solvent PLGA chemistry cell tracking Nanoparticles 0210 nano-technology Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] Biomedical engineering Research Article |
| Zdroj: | ACS Applied Materials & Interfaces Acs Applied Materials & Interfaces., 12, 44, pp. 49335-49345 Acs Applied Materials & Interfaces., 12, 49335-49345 ACS Applied Materials and Interfaces |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | Contains fulltext : 229134.pdf (Publisher’s version ) (Open Access) Perfluorocarbon-loaded nanoparticles are powerful theranostic agents, which are used in the therapy of cancer and stroke and as imaging agents for ultrasound and (19)F magnetic resonance imaging (MRI). Scaling up the production of perfluorocarbon-loaded nanoparticles is essential for clinical translation. However, it represents a major challenge as perfluorocarbons are hydrophobic and lipophobic. We developed a method for continuous-flow production of perfluorocarbon-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles using a modular microfluidic system, with sufficient yields for clinical use. We combined two slit interdigital micromixers with a sonication flow cell to achieve efficient mixing of three phases: liquid perfluorocarbon, PLGA in organic solvent, and aqueous surfactant solution. The production rate was at least 30 times higher than with the conventional formulation. The characteristics of nanoparticles can be adjusted by changing the flow rates and type of solvent, resulting in a high PFC loading of 20-60 wt % and radii below 200 nm. The nanoparticles are nontoxic, suitable for (19)F MRI and ultrasound imaging, and can dissolve oxygen. In vivo (19)F MRI with perfluoro-15-crown-5 ether-loaded nanoparticles showed similar biodistribution as nanoparticles made with the conventional method and a fast clearance from the organs. Overall, we developed a continuous, modular method for scaled-up production of perfluorocarbon-loaded nanoparticles that can be potentially adapted for the production of other multiphase systems. Thus, it will facilitate the clinical translation of theranostic agents in the future. |
| Databáze: | OpenAIRE |
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