Development of medical-grade, discrete, multi-walled carbon nanotubes as drug delivery molecules to enhance the treatment of hematological malignancies
| Autor: | Sophie Harris, Mariah Farrell, Marinkovic Milos, Tasset Aaron Wallace, Michaela R. Reagan, Carolyne Falank, Paul Everill |
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| Rok vydání: | 2019 |
| Předmět: |
Drug
Biocompatibility media_common.quotation_subject Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering macromolecular substances 02 engineering and technology Pharmacology Bone and Bones Article Polyethylene Glycols Mice 03 medical and health sciences Drug Delivery Systems 3T3-L1 Cells medicine Zeta potential Animals Humans Tissue Distribution General Materials Science Doxorubicin Neoplastic transformation Cytotoxicity 030304 developmental biology media_common 0303 health sciences Nanotubes Carbon Chemistry technology industry and agriculture 021001 nanoscience & nanotechnology Burkitt Lymphoma Drug Liberation Hematologic Neoplasms Drug delivery Molecular Medicine Nanocarriers 0210 nano-technology medicine.drug |
| Zdroj: | Nanomedicine |
| ISSN: | 1549-9634 |
| DOI: | 10.1016/j.nano.2019.102025 |
| Popis: | Carbon nanotubes (CNTs) hold great potential as drug delivery transporters given their large drug-binding surface area. Herein, we designed novel, multi-walled, discrete CNTs (dMWCNTs), PEGylated dMWCNTs (PEG-dMWCNTs), and bone-targeting (BT), alendronate-conjugated PEG-dMWCNTs (BT-PEG-dMWCNTs). Using zeta potential, thermogravimetric analysis, TEM, SEM, and FTIR, dMWCNTs were characterized as individual, uniform, and stable. Drug binding and release assays validated dMWCNTs as effective doxorubicin (DOX) transporters. The mass ratio of DOX loading onto dMWCNTs was 35% wt/wt with a ~95% wt/wt efficiency. DOX release was ~51% w/w after 48 hours. Neoplastic transformation, chromosomal aberration, and cytotoxicity assays, confirmed biocompatibility for all dMWCNTs. PEG-dMWCNTs were well tolerated and modulated drug pharmacokinetics in mice. In mice with Burkitt’s lymphoma, DOX-loaded PEG-dMWCNTs and BT-PEG-dMWCNTs reduced tumor burden and increased survival similarly to free drug. Importantly, DOX toxicity was abrogated when DOX was loaded onto PEG-dMWCNTs or BT-PEG-dMWCNTs. Overall, PEG-dMWCNTs and BT-PEG-dMWCNTs represent a promising new nanocarrier platform. |
| Databáze: | OpenAIRE |
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