Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities
Thermosensitive liposomal doxorubicin (TSL-Dox) combined with localized hyperthermia enables targeted drug delivery. Tumor drug uptake occurs only during hyperthermia. We developed a novel method for removal of systemic TSL-Dox remaining after hyperthermia-triggered delivery to reduce toxicities. Th...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/5/1322 |
| _version_ | 1797475457039335424 |
|---|---|
| author | Anjan Motamarry A. Marissa Wolfe Krishna K. Ramajayam Sanket Pattanaik Thomas Benton Yuri Peterson Pegah Faridi Punit Prakash Katherine Twombley Dieter Haemmerich |
| author_facet | Anjan Motamarry A. Marissa Wolfe Krishna K. Ramajayam Sanket Pattanaik Thomas Benton Yuri Peterson Pegah Faridi Punit Prakash Katherine Twombley Dieter Haemmerich |
| author_sort | Anjan Motamarry |
| collection | DOAJ |
| description | Thermosensitive liposomal doxorubicin (TSL-Dox) combined with localized hyperthermia enables targeted drug delivery. Tumor drug uptake occurs only during hyperthermia. We developed a novel method for removal of systemic TSL-Dox remaining after hyperthermia-triggered delivery to reduce toxicities. The carotid artery and jugular vein of Norway brown rats carrying two subcutaneous BN-175 tumors were catheterized. After allowing the animals to recover, TSL-Dox was infused at 7 mg/kg dose. Drug delivery to one of the tumors was performed by inducing 15 min microwave hyperthermia (43 °C). At the end of hyperthermia, an extracorporeal circuit (ECC) comprising a heating module to release drug from TSL-Dox followed by an activated carbon filter to remove free drug was established for 1 h (<i>n</i> = 3). A computational model simulated TSL-Dox pharmacokinetics, including ECC filtration, and predicted cardiac Dox uptake. In animals receiving ECC, we were able to remove 576 ± 65 mg of Dox (29.7 ± 3.7% of the infused dose) within 1 h, with a 2.9-fold reduction of plasma AUC. Fluorescent monitoring enabled real-time quantification of blood concentration and removed drug. Computational modeling predicted that up to 59% of drug could be removed with an ideal filter, and that cardiac uptake can be reduced up to 7×. We demonstrated removal of drug remaining after tumor delivery, reduced plasma AUC, and reduced cardiac uptake, suggesting reduced toxicity. |
| first_indexed | 2024-03-09T20:44:23Z |
| format | Article |
| id | doaj.art-16a65b81655240588f957d94d8c83a65 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:44:23Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-16a65b81655240588f957d94d8c83a652023-11-23T22:49:14ZengMDPI AGCancers2072-66942022-03-01145132210.3390/cancers14051322Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce ToxicitiesAnjan Motamarry0A. Marissa Wolfe1Krishna K. Ramajayam2Sanket Pattanaik3Thomas Benton4Yuri Peterson5Pegah Faridi6Punit Prakash7Katherine Twombley8Dieter Haemmerich9Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USARalph H. Johnson VA Medical Center, Charleston, SC 29425, USADepartment of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Electrical and Computer Engineering, Kansas State University, Manhattan, KS 66506, USADepartment of Electrical and Computer Engineering, Kansas State University, Manhattan, KS 66506, USADepartment of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USAThermosensitive liposomal doxorubicin (TSL-Dox) combined with localized hyperthermia enables targeted drug delivery. Tumor drug uptake occurs only during hyperthermia. We developed a novel method for removal of systemic TSL-Dox remaining after hyperthermia-triggered delivery to reduce toxicities. The carotid artery and jugular vein of Norway brown rats carrying two subcutaneous BN-175 tumors were catheterized. After allowing the animals to recover, TSL-Dox was infused at 7 mg/kg dose. Drug delivery to one of the tumors was performed by inducing 15 min microwave hyperthermia (43 °C). At the end of hyperthermia, an extracorporeal circuit (ECC) comprising a heating module to release drug from TSL-Dox followed by an activated carbon filter to remove free drug was established for 1 h (<i>n</i> = 3). A computational model simulated TSL-Dox pharmacokinetics, including ECC filtration, and predicted cardiac Dox uptake. In animals receiving ECC, we were able to remove 576 ± 65 mg of Dox (29.7 ± 3.7% of the infused dose) within 1 h, with a 2.9-fold reduction of plasma AUC. Fluorescent monitoring enabled real-time quantification of blood concentration and removed drug. Computational modeling predicted that up to 59% of drug could be removed with an ideal filter, and that cardiac uptake can be reduced up to 7×. We demonstrated removal of drug remaining after tumor delivery, reduced plasma AUC, and reduced cardiac uptake, suggesting reduced toxicity.https://www.mdpi.com/2072-6694/14/5/1322thermosensitive liposomeshyperthermiaextracorporeal circulation |
| spellingShingle | Anjan Motamarry A. Marissa Wolfe Krishna K. Ramajayam Sanket Pattanaik Thomas Benton Yuri Peterson Pegah Faridi Punit Prakash Katherine Twombley Dieter Haemmerich Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities Cancers thermosensitive liposomes hyperthermia extracorporeal circulation |
| title | Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities |
| title_full | Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities |
| title_fullStr | Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities |
| title_full_unstemmed | Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities |
| title_short | Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities |
| title_sort | extracorporeal removal of thermosensitive liposomal doxorubicin from systemic circulation after tumor delivery to reduce toxicities |
| topic | thermosensitive liposomes hyperthermia extracorporeal circulation |
| url | https://www.mdpi.com/2072-6694/14/5/1322 |
| work_keys_str_mv | AT anjanmotamarry extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT amarissawolfe extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT krishnakramajayam extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT sanketpattanaik extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT thomasbenton extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT yuripeterson extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT pegahfaridi extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT punitprakash extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT katherinetwombley extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities AT dieterhaemmerich extracorporealremovalofthermosensitiveliposomaldoxorubicinfromsystemiccirculationaftertumordeliverytoreducetoxicities |