Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen
Co-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Polymers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4360/14/8/1568 |
| _version_ | 1797409520896442368 |
|---|---|
| author | Raj Patel Quezia Lacerda Brian E. Oeffinger John R. Eisenbrey Ankit K. Rochani Gagan Kaushal Corinne E. Wessner Margaret A. Wheatley |
| author_facet | Raj Patel Quezia Lacerda Brian E. Oeffinger John R. Eisenbrey Ankit K. Rochani Gagan Kaushal Corinne E. Wessner Margaret A. Wheatley |
| author_sort | Raj Patel |
| collection | DOAJ |
| description | Co-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabilized microbubbles encapsulating lonidamine, with the aim of developing an agent containing both a therapeutic gas and two drugs acting in combination. Upon comparison of unloaded, single-loaded, and dual-loaded microbubbles, size (~1.7 µm) and yield (~2 × 10<sup>9</sup> microbubbles/mL) (~1.7) were not statistically different, nor were acoustic properties (maximum in vitro enhancements roughly 18 dB, in vitro enhancements roughly 18 dB). Both drugs encapsulated above required doses calculated for head and neck squamous cell carcinoma, the cancer of choice. Interestingly, paclitaxel encapsulation efficiency increased from 1.66% to 3.48% when lonidamine was included. During preparation, the combination of single drug-loaded micelles gave higher encapsulation (µg drug/g microbubbles) than micelles loaded with either drug alone (lonidamine, 104.85 ± 22.87 vs. 87.54 ± 16.41), paclitaxel (187.35 ± 8.38 vs. 136.51 ± 30.66). In vivo intravenous microbubbles produced prompt ultrasound enhancement within tumors lasting 3–5 min, indicating penetration into tumor vasculature. The ability to locally destroy the microbubble within the tumor vasculature was confirmed using a series of higher intensity ultrasound pulses. This ability to locally destroy microbubbles shows therapeutic promise that warrants further investigation. |
| first_indexed | 2024-03-09T04:16:47Z |
| format | Article |
| id | doaj.art-27b783d8650349fc824dd869a5a9cee0 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-09T04:16:47Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-27b783d8650349fc824dd869a5a9cee02023-12-03T13:52:35ZengMDPI AGPolymers2073-43602022-04-01148156810.3390/polym14081568Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing OxygenRaj Patel0Quezia Lacerda1Brian E. Oeffinger2John R. Eisenbrey3Ankit K. Rochani4Gagan Kaushal5Corinne E. Wessner6Margaret A. Wheatley7School of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PA 19104, USASchool of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PA 19104, USASchool of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PA 19104, USADepartment of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Pharmaceutical Sciences, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Pharmaceutical Sciences, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USASchool of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PA 19104, USACo-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabilized microbubbles encapsulating lonidamine, with the aim of developing an agent containing both a therapeutic gas and two drugs acting in combination. Upon comparison of unloaded, single-loaded, and dual-loaded microbubbles, size (~1.7 µm) and yield (~2 × 10<sup>9</sup> microbubbles/mL) (~1.7) were not statistically different, nor were acoustic properties (maximum in vitro enhancements roughly 18 dB, in vitro enhancements roughly 18 dB). Both drugs encapsulated above required doses calculated for head and neck squamous cell carcinoma, the cancer of choice. Interestingly, paclitaxel encapsulation efficiency increased from 1.66% to 3.48% when lonidamine was included. During preparation, the combination of single drug-loaded micelles gave higher encapsulation (µg drug/g microbubbles) than micelles loaded with either drug alone (lonidamine, 104.85 ± 22.87 vs. 87.54 ± 16.41), paclitaxel (187.35 ± 8.38 vs. 136.51 ± 30.66). In vivo intravenous microbubbles produced prompt ultrasound enhancement within tumors lasting 3–5 min, indicating penetration into tumor vasculature. The ability to locally destroy the microbubble within the tumor vasculature was confirmed using a series of higher intensity ultrasound pulses. This ability to locally destroy microbubbles shows therapeutic promise that warrants further investigation.https://www.mdpi.com/2073-4360/14/8/1568ultrasound contrast agentmicrobubblestheranostic agentsultrasound-triggered drug deliverydual drug loadingsurfactant |
| spellingShingle | Raj Patel Quezia Lacerda Brian E. Oeffinger John R. Eisenbrey Ankit K. Rochani Gagan Kaushal Corinne E. Wessner Margaret A. Wheatley Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen Polymers ultrasound contrast agent microbubbles theranostic agents ultrasound-triggered drug delivery dual drug loading surfactant |
| title | Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen |
| title_full | Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen |
| title_fullStr | Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen |
| title_full_unstemmed | Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen |
| title_short | Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen |
| title_sort | development of a dual drug loaded surfactant stabilized contrast agent containing oxygen |
| topic | ultrasound contrast agent microbubbles theranostic agents ultrasound-triggered drug delivery dual drug loading surfactant |
| url | https://www.mdpi.com/2073-4360/14/8/1568 |
| work_keys_str_mv | AT rajpatel developmentofadualdrugloadedsurfactantstabilizedcontrastagentcontainingoxygen AT quezialacerda developmentofadualdrugloadedsurfactantstabilizedcontrastagentcontainingoxygen AT brianeoeffinger developmentofadualdrugloadedsurfactantstabilizedcontrastagentcontainingoxygen AT johnreisenbrey developmentofadualdrugloadedsurfactantstabilizedcontrastagentcontainingoxygen AT ankitkrochani developmentofadualdrugloadedsurfactantstabilizedcontrastagentcontainingoxygen AT gagankaushal developmentofadualdrugloadedsurfactantstabilizedcontrastagentcontainingoxygen AT corinneewessner developmentofadualdrugloadedsurfactantstabilizedcontrastagentcontainingoxygen AT margaretawheatley developmentofadualdrugloadedsurfactantstabilizedcontrastagentcontainingoxygen |