The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers
The combination of ultrasound and microbubbles (USMB) has been applied to enhance drug permeability across tissue barriers. Most studies focused on only one physicochemical aspect (i.e., molecular weight of the delivered molecule). Using an in vitro epithelial (MDCK II) cell barrier, we examined the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/3/494 |
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| author | Charis Rousou Josanne de Maar Boning Qiu Kim van der Wurff-Jacobs Marika Ruponen Arto Urtti Sabrina Oliveira Chrit Moonen Gert Storm Enrico Mastrobattista Roel Deckers |
| author_facet | Charis Rousou Josanne de Maar Boning Qiu Kim van der Wurff-Jacobs Marika Ruponen Arto Urtti Sabrina Oliveira Chrit Moonen Gert Storm Enrico Mastrobattista Roel Deckers |
| author_sort | Charis Rousou |
| collection | DOAJ |
| description | The combination of ultrasound and microbubbles (USMB) has been applied to enhance drug permeability across tissue barriers. Most studies focused on only one physicochemical aspect (i.e., molecular weight of the delivered molecule). Using an in vitro epithelial (MDCK II) cell barrier, we examined the effects of USMB on the permeability of five molecules varying in molecular weight (182 Da to 20 kDa) and hydrophilicity (LogD at pH 7.4 from 1.5 to highly hydrophilic). Treatment of cells with USMB at increasing ultrasound pressures did not have a significant effect on the permeability of small molecules (molecular weight 259 to 376 Da), despite their differences in hydrophilicity (LogD at pH 7.4 from −3.2 to 1.5). The largest molecules (molecular weight 4 and 20 kDa) showed the highest increase in the epithelial permeability (3-7-fold). Simultaneously, USMB enhanced intracellular accumulation of the same molecules. In the case of the clinically relevant anti- C-X-C Chemokine Receptor Type 4 (CXCR4) nanobody (molecular weight 15 kDa), USMB enhanced paracellular permeability by two-fold and increased binding to retinoblastoma cells by five-fold. Consequently, USMB is a potential tool to improve the efficacy and safety of the delivery of drugs to organs protected by tissue barriers, such as the eye and the brain. |
| first_indexed | 2024-03-09T12:59:48Z |
| format | Article |
| id | doaj.art-617e21bbdeb14c44b399418198e81166 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:59:48Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-617e21bbdeb14c44b399418198e811662023-11-30T21:55:42ZengMDPI AGPharmaceutics1999-49232022-02-0114349410.3390/pharmaceutics14030494The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell BarriersCharis Rousou0Josanne de Maar1Boning Qiu2Kim van der Wurff-Jacobs3Marika Ruponen4Arto Urtti5Sabrina Oliveira6Chrit Moonen7Gert Storm8Enrico Mastrobattista9Roel Deckers10Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Heidelberglaan 8, 3584 CS Utrecht, The NetherlandsImaging and Oncology Division, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The NetherlandsDepartment of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Heidelberglaan 8, 3584 CS Utrecht, The NetherlandsDepartment of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Heidelberglaan 8, 3584 CS Utrecht, The NetherlandsSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, FinlandSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, FinlandDepartment of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Heidelberglaan 8, 3584 CS Utrecht, The NetherlandsImaging and Oncology Division, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The NetherlandsDepartment of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Heidelberglaan 8, 3584 CS Utrecht, The NetherlandsDepartment of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Heidelberglaan 8, 3584 CS Utrecht, The NetherlandsImaging and Oncology Division, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The NetherlandsThe combination of ultrasound and microbubbles (USMB) has been applied to enhance drug permeability across tissue barriers. Most studies focused on only one physicochemical aspect (i.e., molecular weight of the delivered molecule). Using an in vitro epithelial (MDCK II) cell barrier, we examined the effects of USMB on the permeability of five molecules varying in molecular weight (182 Da to 20 kDa) and hydrophilicity (LogD at pH 7.4 from 1.5 to highly hydrophilic). Treatment of cells with USMB at increasing ultrasound pressures did not have a significant effect on the permeability of small molecules (molecular weight 259 to 376 Da), despite their differences in hydrophilicity (LogD at pH 7.4 from −3.2 to 1.5). The largest molecules (molecular weight 4 and 20 kDa) showed the highest increase in the epithelial permeability (3-7-fold). Simultaneously, USMB enhanced intracellular accumulation of the same molecules. In the case of the clinically relevant anti- C-X-C Chemokine Receptor Type 4 (CXCR4) nanobody (molecular weight 15 kDa), USMB enhanced paracellular permeability by two-fold and increased binding to retinoblastoma cells by five-fold. Consequently, USMB is a potential tool to improve the efficacy and safety of the delivery of drugs to organs protected by tissue barriers, such as the eye and the brain.https://www.mdpi.com/1999-4923/14/3/494ultrasoundmicrobubblesepithelial permeationparacellular permeabilityintracellular accumulationnanobody |
| spellingShingle | Charis Rousou Josanne de Maar Boning Qiu Kim van der Wurff-Jacobs Marika Ruponen Arto Urtti Sabrina Oliveira Chrit Moonen Gert Storm Enrico Mastrobattista Roel Deckers The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers Pharmaceutics ultrasound microbubbles epithelial permeation paracellular permeability intracellular accumulation nanobody |
| title | The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers |
| title_full | The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers |
| title_fullStr | The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers |
| title_full_unstemmed | The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers |
| title_short | The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers |
| title_sort | effect of microbubble assisted ultrasound on molecular permeability across cell barriers |
| topic | ultrasound microbubbles epithelial permeation paracellular permeability intracellular accumulation nanobody |
| url | https://www.mdpi.com/1999-4923/14/3/494 |
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