Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors
Abstract Central Nervous System (CNS) malignant tumors are a leading cause of death worldwide with a high mortality rate. While numerous strategies have been proposed to treat CNS tumors, the treatment efficacy is still low mainly due to the existence of the Blood–Brain Barrier (BBB). BBB is a natur...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-23429-w |
| _version_ | 1811230448805740544 |
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| author | Ahmad Boroumand Mehrnoush Mehrarya Ashkan Ghanbarzadeh-Dagheyan Mohammad Taghi Ahmadian |
| author_facet | Ahmad Boroumand Mehrnoush Mehrarya Ashkan Ghanbarzadeh-Dagheyan Mohammad Taghi Ahmadian |
| author_sort | Ahmad Boroumand |
| collection | DOAJ |
| description | Abstract Central Nervous System (CNS) malignant tumors are a leading cause of death worldwide with a high mortality rate. While numerous strategies have been proposed to treat CNS tumors, the treatment efficacy is still low mainly due to the existence of the Blood–Brain Barrier (BBB). BBB is a natural cellular layer between the circulatory system and brain extracellular fluid, limiting the transfer of drug particles and confining the routine treatment strategies in which drugs are released in the blood. Consequently, direct drug delivery methods have been devised to bypass the BBB. However, the efficiency of these methods is not enough to treat deep and large brain tumors. In the study at hand, the effect of focused ultrasound (FUS) waves on enhancing drug delivery to brain tumors, through ultrasound-assisted convection-enhanced delivery (UCED), has been investigated. First, brain mimicking gels were synthesized to mimic the CNS microenvironment, and the drug solution was injected into them. Second, FUS waves with the resonance frequency of 1.1 MHz were applied to the drug injected zone. Next, a finite element (FE) model was developed to evaluate the pre-existing equation in the literature for describing the drug delivery via acoustic streaming in brain tissue. Experimental results showed that the FUS transducer was able to enhance the drug volume distribution up to 500% relative to convection-enhanced delivery alone (CED). Numerical analysis showed that the FE model could replicate the experimental penetration depths with a mean difference value of less than 21%, and acoustic streaming plays a significant role in UCED. Therefore, the results of this study could open a new way to develop FE models of the brain to better evaluate the UCED and reduce the costs of conducting clinical and animal studies. |
| first_indexed | 2024-04-12T10:29:30Z |
| format | Article |
| id | doaj.art-a1b9db4adbd446ff8514f0d2511677b5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T10:29:30Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a1b9db4adbd446ff8514f0d2511677b52022-12-22T03:36:53ZengNature PortfolioScientific Reports2045-23222022-11-0112111110.1038/s41598-022-23429-wNumerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumorsAhmad Boroumand0Mehrnoush Mehrarya1Ashkan Ghanbarzadeh-Dagheyan2Mohammad Taghi Ahmadian3School of Mechanical Engineering, Sharif University of TechnologyProtein Research Center, Shahid Beheshti UniversitySchool of Mechanical Engineering, Sharif University of TechnologySchool of Mechanical Engineering, Sharif University of TechnologyAbstract Central Nervous System (CNS) malignant tumors are a leading cause of death worldwide with a high mortality rate. While numerous strategies have been proposed to treat CNS tumors, the treatment efficacy is still low mainly due to the existence of the Blood–Brain Barrier (BBB). BBB is a natural cellular layer between the circulatory system and brain extracellular fluid, limiting the transfer of drug particles and confining the routine treatment strategies in which drugs are released in the blood. Consequently, direct drug delivery methods have been devised to bypass the BBB. However, the efficiency of these methods is not enough to treat deep and large brain tumors. In the study at hand, the effect of focused ultrasound (FUS) waves on enhancing drug delivery to brain tumors, through ultrasound-assisted convection-enhanced delivery (UCED), has been investigated. First, brain mimicking gels were synthesized to mimic the CNS microenvironment, and the drug solution was injected into them. Second, FUS waves with the resonance frequency of 1.1 MHz were applied to the drug injected zone. Next, a finite element (FE) model was developed to evaluate the pre-existing equation in the literature for describing the drug delivery via acoustic streaming in brain tissue. Experimental results showed that the FUS transducer was able to enhance the drug volume distribution up to 500% relative to convection-enhanced delivery alone (CED). Numerical analysis showed that the FE model could replicate the experimental penetration depths with a mean difference value of less than 21%, and acoustic streaming plays a significant role in UCED. Therefore, the results of this study could open a new way to develop FE models of the brain to better evaluate the UCED and reduce the costs of conducting clinical and animal studies.https://doi.org/10.1038/s41598-022-23429-w |
| spellingShingle | Ahmad Boroumand Mehrnoush Mehrarya Ashkan Ghanbarzadeh-Dagheyan Mohammad Taghi Ahmadian Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors Scientific Reports |
| title | Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors |
| title_full | Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors |
| title_fullStr | Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors |
| title_full_unstemmed | Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors |
| title_short | Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors |
| title_sort | numerical and experimental evaluation of ultrasound assisted convection enhanced delivery to transfer drugs into brain tumors |
| url | https://doi.org/10.1038/s41598-022-23429-w |
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