Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow Device
Polymeric particles are ideal drug delivery systems due to their cellular uptake-relevant size. Microparticles could be developed for direct injection of drug formulations into a diseased site, such as a tumor, allowing for drug retention and slow drug exposure over time through sustained release me...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/4/890 |
| _version_ | 1819135419387740160 |
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| author | Natalia Vargas Montoya Rachel Peterson Kimberly J. Ornell Dirk R. Albrecht Jeannine M. Coburn |
| author_facet | Natalia Vargas Montoya Rachel Peterson Kimberly J. Ornell Dirk R. Albrecht Jeannine M. Coburn |
| author_sort | Natalia Vargas Montoya |
| collection | DOAJ |
| description | Polymeric particles are ideal drug delivery systems due to their cellular uptake-relevant size. Microparticles could be developed for direct injection of drug formulations into a diseased site, such as a tumor, allowing for drug retention and slow drug exposure over time through sustained release mechanisms. <i>Bombyx mori</i> silk fibroin has shown promise as a biocompatible biomaterial both in research and the clinic. Silk has been previously used to make particles using an emulsion-based method with poly(vinyl alcohol) (PVA). In this study, polydimethylsiloxane-based microfluidic devices were designed, fabricated, and characterized to produce silk particles through self-association of silk when exposed to PVA. Three main variables resulted in differences in particle size and size distribution, or polydispersity index (PDI). Utilizing a co-flow microfluidic device decreased the PDI of the silk particles as compared to an emulsion-based method (0.13 versus 0.65, respectively). With a flow-focusing microfluidics device, lowering the silk flow rate from 0.80 to 0.06 mL/h resulted in a decrease in the median particle size from 6.8 to 3.0 μm and the PDI from 0.12 to 0.05, respectively. Lastly, decreasing the silk concentration from 12% to 2% resulted in a decrease in the median particle size from 5.6 to 2.8 μm and the PDI from 0.81 to 0.25, respectively. Binding and release of doxorubicin, a cytotoxic drug commonly used for cancer treatment, with the fabricated silk particles was evaluated. Doxorubicin loading in the silk particles was approximately 41 µg/mg; sustained doxorubicin release occurred over 23 days. When the cytotoxicity of the released doxorubicin was tested on KELLY neuroblastoma cells, significant cell death was observed. To demonstrate the potential for internalization of the silk particles, both KELLY and THP-1-derived macrophages were exposed to fluorescently labelled silk particles for up to 24 h. With the macrophages, internalization of the silk particles was observed. Additionally, THP-1 derived macrophages exposure to silk particles increased TNF-α secretion. Overall, this microfluidics-based approach for fabricating silk particles utilizing PVA as a means to induce phase separation and silk self-assembly is a promising approach to control particle size and size distribution. These silk particles may be utilized for a variety of biomedical applications including drug delivery to multiple cell types within a tumor microenvironment. |
| first_indexed | 2024-12-22T10:18:47Z |
| format | Article |
| id | doaj.art-ff8bc6d3cc12421b939015a0f359b0f4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T10:18:47Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ff8bc6d3cc12421b939015a0f359b0f42022-12-21T18:29:41ZengMDPI AGMolecules1420-30492020-02-0125489010.3390/molecules25040890molecules25040890Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow DeviceNatalia Vargas Montoya0Rachel Peterson1Kimberly J. Ornell2Dirk R. Albrecht3Jeannine M. Coburn4Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USADepartment of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USADepartment of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USADepartment of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USADepartment of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USAPolymeric particles are ideal drug delivery systems due to their cellular uptake-relevant size. Microparticles could be developed for direct injection of drug formulations into a diseased site, such as a tumor, allowing for drug retention and slow drug exposure over time through sustained release mechanisms. <i>Bombyx mori</i> silk fibroin has shown promise as a biocompatible biomaterial both in research and the clinic. Silk has been previously used to make particles using an emulsion-based method with poly(vinyl alcohol) (PVA). In this study, polydimethylsiloxane-based microfluidic devices were designed, fabricated, and characterized to produce silk particles through self-association of silk when exposed to PVA. Three main variables resulted in differences in particle size and size distribution, or polydispersity index (PDI). Utilizing a co-flow microfluidic device decreased the PDI of the silk particles as compared to an emulsion-based method (0.13 versus 0.65, respectively). With a flow-focusing microfluidics device, lowering the silk flow rate from 0.80 to 0.06 mL/h resulted in a decrease in the median particle size from 6.8 to 3.0 μm and the PDI from 0.12 to 0.05, respectively. Lastly, decreasing the silk concentration from 12% to 2% resulted in a decrease in the median particle size from 5.6 to 2.8 μm and the PDI from 0.81 to 0.25, respectively. Binding and release of doxorubicin, a cytotoxic drug commonly used for cancer treatment, with the fabricated silk particles was evaluated. Doxorubicin loading in the silk particles was approximately 41 µg/mg; sustained doxorubicin release occurred over 23 days. When the cytotoxicity of the released doxorubicin was tested on KELLY neuroblastoma cells, significant cell death was observed. To demonstrate the potential for internalization of the silk particles, both KELLY and THP-1-derived macrophages were exposed to fluorescently labelled silk particles for up to 24 h. With the macrophages, internalization of the silk particles was observed. Additionally, THP-1 derived macrophages exposure to silk particles increased TNF-α secretion. Overall, this microfluidics-based approach for fabricating silk particles utilizing PVA as a means to induce phase separation and silk self-assembly is a promising approach to control particle size and size distribution. These silk particles may be utilized for a variety of biomedical applications including drug delivery to multiple cell types within a tumor microenvironment.https://www.mdpi.com/1420-3049/25/4/890microfluidicssilk fibroinparticlespoly(vinyl alcohol)drug deliverymacrophagesphase separation |
| spellingShingle | Natalia Vargas Montoya Rachel Peterson Kimberly J. Ornell Dirk R. Albrecht Jeannine M. Coburn Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow Device Molecules microfluidics silk fibroin particles poly(vinyl alcohol) drug delivery macrophages phase separation |
| title | Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow Device |
| title_full | Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow Device |
| title_fullStr | Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow Device |
| title_full_unstemmed | Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow Device |
| title_short | Silk Particle Production Based on Silk/PVA Phase Separation Using a Microfabricated Co-flow Device |
| title_sort | silk particle production based on silk pva phase separation using a microfabricated co flow device |
| topic | microfluidics silk fibroin particles poly(vinyl alcohol) drug delivery macrophages phase separation |
| url | https://www.mdpi.com/1420-3049/25/4/890 |
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