Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs
Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet non-specific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treat...
| Main Authors: | , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2017
|
| Online Access: | http://hdl.handle.net/1721.1/108647 https://orcid.org/0000-0001-6694-6761 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0002-7836-415X |
| _version_ | 1826201614285799424 |
|---|---|
| author | Schoellhammer, Carl Magnus Srinivasan, Sharanya Barman, Ross Mo, Stacy H. Langer, Robert S Polat, Baris E. Blankschtein, Daniel |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Schoellhammer, Carl Magnus Srinivasan, Sharanya Barman, Ross Mo, Stacy H. Langer, Robert S Polat, Baris E. Blankschtein, Daniel |
| author_sort | Schoellhammer, Carl Magnus |
| collection | MIT |
| description | Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet non-specific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20 kHz and 1 MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20 kHz alone. Additionally, LTRs generated by treatment with 20 kHz + 1 MHz were found to be more permeable than those generated with 20 kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20 kHz + 1 MHz were calculated to be significantly larger than the pores in skin treated with 20 kHz alone. This demonstrates for the first time that LTRs generated with 20 kHz + 1 MHz are also more permeable than those generated with 20 kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20 kHz + 1 MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20 kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo. |
| first_indexed | 2024-09-23T11:54:08Z |
| format | Article |
| id | mit-1721.1/108647 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:54:08Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1086472022-09-27T22:44:30Z Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs Schoellhammer, Carl Magnus Srinivasan, Sharanya Barman, Ross Mo, Stacy H. Langer, Robert S Polat, Baris E. Blankschtein, Daniel Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Koch Institute for Integrative Cancer Research at MIT Schoellhammer, Carl Magnus Srinivasan, Sharanya Barman, Ross Mo, Stacy H. Polat, Baris Erinc Langer, Robert S Blankschtein, Edmundo D Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet non-specific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20 kHz and 1 MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20 kHz alone. Additionally, LTRs generated by treatment with 20 kHz + 1 MHz were found to be more permeable than those generated with 20 kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20 kHz + 1 MHz were calculated to be significantly larger than the pores in skin treated with 20 kHz alone. This demonstrates for the first time that LTRs generated with 20 kHz + 1 MHz are also more permeable than those generated with 20 kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20 kHz + 1 MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20 kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo. National Institutes of Health (U.S.) (Grant EB-00351) National Institutes of Health (U.S.) (Grant CA014051) 2017-05-03T19:39:58Z 2017-05-03T19:39:58Z 2015-02 2014-09 Article http://purl.org/eprint/type/JournalArticle 0168-3659 http://hdl.handle.net/1721.1/108647 Schoellhammer, Carl M. et al. “Applicability and Safety of Dual-Frequency Ultrasonic Treatment for the Transdermal Delivery of Drugs.” Journal of Controlled Release 202 (2015): 93–100. https://orcid.org/0000-0001-6694-6761 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0002-7836-415X en_US http://dx.doi.org/10.1016/j.jconrel.2015.02.002 Journal of Controlled Release Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Schoellhammer, Carl Magnus Srinivasan, Sharanya Barman, Ross Mo, Stacy H. Langer, Robert S Polat, Baris E. Blankschtein, Daniel Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs |
| title | Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs |
| title_full | Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs |
| title_fullStr | Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs |
| title_full_unstemmed | Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs |
| title_short | Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs |
| title_sort | applicability and safety of dual frequency ultrasonic treatment for the transdermal delivery of drugs |
| url | http://hdl.handle.net/1721.1/108647 https://orcid.org/0000-0001-6694-6761 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0002-7836-415X |
| work_keys_str_mv | AT schoellhammercarlmagnus applicabilityandsafetyofdualfrequencyultrasonictreatmentforthetransdermaldeliveryofdrugs AT srinivasansharanya applicabilityandsafetyofdualfrequencyultrasonictreatmentforthetransdermaldeliveryofdrugs AT barmanross applicabilityandsafetyofdualfrequencyultrasonictreatmentforthetransdermaldeliveryofdrugs AT mostacyh applicabilityandsafetyofdualfrequencyultrasonictreatmentforthetransdermaldeliveryofdrugs AT langerroberts applicabilityandsafetyofdualfrequencyultrasonictreatmentforthetransdermaldeliveryofdrugs AT polatbarise applicabilityandsafetyofdualfrequencyultrasonictreatmentforthetransdermaldeliveryofdrugs AT blankschteindaniel applicabilityandsafetyofdualfrequencyultrasonictreatmentforthetransdermaldeliveryofdrugs |