Oral Codelivery of WR-1065 Using Curcumin-Linked ROS-Sensitive Nanoparticles for Synergistic Radioprotection
Autor: | Xinxin Wang, Xiaona Lin, Renbin Yuan, Hongqi Tian, Xuejiao Li, Yahong Liu, Yuying Guo, Longfei Miao |
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Rok vydání: | 2021 |
Předmět: |
Active ingredient
Curcumin Biocompatibility 0206 medical engineering Biomedical Engineering 02 engineering and technology Amifostine Pharmacology 021001 nanoscience & nanotechnology 020601 biomedical engineering Mercaptoethylamines Bioavailability Biomaterials chemistry.chemical_compound chemistry Drug delivery medicine Nanoparticles Nanocarriers Reactive Oxygen Species 0210 nano-technology Ethylene glycol medicine.drug |
Zdroj: | ACS Biomaterials Science & Engineering. 7:2496-2507 |
ISSN: | 2373-9878 |
Popis: | Protecting the body from radiation damage is a huge medical challenge. Amifostine and curcumin are both effective radioprotectants, but their use has been greatly restricted due to various reasons including low bioavailability. Nanoscale drug delivery systems of poly(ethylene glycol)-poly(ε-caprolactone) copolymers can improve the bioavailability of drugs due to excellent biocompatibility, biodegradability, and long circulation characteristics. In this study, a new reactive oxygen species-sensitive nanocarrier fabricated by linking curcumin and thioketal to poly(ethylene glycol)-poly(ε-caprolactone) polymer was used for delivery of WR-1065 (the active ingredient of amifostine). The content of curcumin in this polymer was about 7.6%, and the drug loading of WR-1065 was 44%. The WR-1065-loaded nanoparticles (NPs) had an average size of 128.6 nm and uniform spherical morphology. These WR-1065-loaded NPs reduced the metabolism of curcumin and WR-1065 in the gastrointestinal tract and could be well absorbed by cells and distributed to multiple organs. Compared with a single drug, oral administration of WR-1065-loaded NPs demonstrated obvious radioprotective effects on the hematopoietic system and prevented intestinal injury. The 30-day survival rate after half-lethal dose (7.2 Gy) of total body irradiation was 100%. In general, WR-1065-loaded NPs improved the oral bioavailability of WR-1065 and curcumin. This multifunctional nanocarrier provides a possibility for combination therapy in treating ionizing radiation damage. |
Databáze: | OpenAIRE |
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