One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique
The use of exosomes encapsulating therapeutic agents for the treatment of diseases is of increasing interest. However, some concerns such as limited efficiency and scalability of conventional drug encapsulation methods to exosomes have still remained; thus, a new approach that enables encapsulation...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/1/108 |
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| author | Tatsuya Fukuta Mayumi Ikeda-Imafuku Satoshi Kodama Junko Kuse Ko Matsui Yasunori Iwao |
| author_facet | Tatsuya Fukuta Mayumi Ikeda-Imafuku Satoshi Kodama Junko Kuse Ko Matsui Yasunori Iwao |
| author_sort | Tatsuya Fukuta |
| collection | DOAJ |
| description | The use of exosomes encapsulating therapeutic agents for the treatment of diseases is of increasing interest. However, some concerns such as limited efficiency and scalability of conventional drug encapsulation methods to exosomes have still remained; thus, a new approach that enables encapsulation of therapeutic agents with superior efficiency and scalability is required. Herein, we used RAW264 macrophage cell-derived exosomes (RAW-Exos) and demonstrated that high-pressure homogenization (HPH) using a microfluidizer decreased their particle size without changing their morphology, the amount of exosomal marker proteins, and cellular uptake efficiency into RAW264 and colon-26 cancer cells. Moreover, HPH allowed for modification of polyethylene glycol (PEG)-conjugated lipids onto RAW-Exos, as well as encapsulation of the anti-cancer agent doxorubicin. Importantly, the doxorubicin encapsulation efficiency became higher upon increasing the process pressure and simultaneous HPH with PEG-lipids. Moreover, treatment with PEG-modified RAW-Exos encapsulating doxorubicin significantly suppressed tumor growth in colon-26-bearing mice. Taken together, these results suggest that HPH using a microfluidizer could be useful to prepare PEG-modified Exos encapsulating anti-cancer drugs via a one-step pharmaceutical process, and that the prepared functional Exos could be applied for the treatment of cancer in vivo. |
| first_indexed | 2024-03-09T11:28:24Z |
| format | Article |
| id | doaj.art-54bcc1e3b2c748578f13fc1ab9ea59f2 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T11:28:24Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-54bcc1e3b2c748578f13fc1ab9ea59f22023-11-30T23:55:55ZengMDPI AGPharmaceuticals1424-82472023-01-0116110810.3390/ph16010108One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization TechniqueTatsuya Fukuta0Mayumi Ikeda-Imafuku1Satoshi Kodama2Junko Kuse3Ko Matsui4Yasunori Iwao5Department of Physical Pharmaceutics, School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shichiban-Cho, Wakayama 640-8156, JapanDepartment of Physical Pharmaceutics, School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shichiban-Cho, Wakayama 640-8156, JapanPowrex Corporation, 5-5-5 Kita-Gawara, Itami 664-0837, Hyogo, JapanPowrex Corporation, 5-5-5 Kita-Gawara, Itami 664-0837, Hyogo, JapanPowrex Corporation, 5-5-5 Kita-Gawara, Itami 664-0837, Hyogo, JapanDepartment of Physical Pharmaceutics, School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shichiban-Cho, Wakayama 640-8156, JapanThe use of exosomes encapsulating therapeutic agents for the treatment of diseases is of increasing interest. However, some concerns such as limited efficiency and scalability of conventional drug encapsulation methods to exosomes have still remained; thus, a new approach that enables encapsulation of therapeutic agents with superior efficiency and scalability is required. Herein, we used RAW264 macrophage cell-derived exosomes (RAW-Exos) and demonstrated that high-pressure homogenization (HPH) using a microfluidizer decreased their particle size without changing their morphology, the amount of exosomal marker proteins, and cellular uptake efficiency into RAW264 and colon-26 cancer cells. Moreover, HPH allowed for modification of polyethylene glycol (PEG)-conjugated lipids onto RAW-Exos, as well as encapsulation of the anti-cancer agent doxorubicin. Importantly, the doxorubicin encapsulation efficiency became higher upon increasing the process pressure and simultaneous HPH with PEG-lipids. Moreover, treatment with PEG-modified RAW-Exos encapsulating doxorubicin significantly suppressed tumor growth in colon-26-bearing mice. Taken together, these results suggest that HPH using a microfluidizer could be useful to prepare PEG-modified Exos encapsulating anti-cancer drugs via a one-step pharmaceutical process, and that the prepared functional Exos could be applied for the treatment of cancer in vivo.https://www.mdpi.com/1424-8247/16/1/108extracellular vesiclesexosomeshigh-pressure homogenizationmicrofluidizerDDSanti-cancer drugs |
| spellingShingle | Tatsuya Fukuta Mayumi Ikeda-Imafuku Satoshi Kodama Junko Kuse Ko Matsui Yasunori Iwao One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique Pharmaceuticals extracellular vesicles exosomes high-pressure homogenization microfluidizer DDS anti-cancer drugs |
| title | One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique |
| title_full | One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique |
| title_fullStr | One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique |
| title_full_unstemmed | One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique |
| title_short | One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique |
| title_sort | one step pharmaceutical preparation of peg modified exosomes encapsulating anti cancer drugs by a high pressure homogenization technique |
| topic | extracellular vesicles exosomes high-pressure homogenization microfluidizer DDS anti-cancer drugs |
| url | https://www.mdpi.com/1424-8247/16/1/108 |
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