Chapter 11 Conclusion
11.3 Thermal sensitive Ferrogel (Pluronic®)
1. Novel thermo-sensitive ferrofluids were successfully synthesized with core-shell NMPs and F127-fluids, and can be modulated by temperature changes to form ferrogels.
2. By its thermo-triggered operations and higher drug uptake properties, it is potential that this typed F127-ferrofluids can be applied as a biomedicine application, such as drug carriers.
3. The dual-functional (magnetic/thermal) drug carriers were successfully fabricated by in-situ and self-assembly process, and the core-shell structure was examined by TEM, XRD, Raman spectra and XPS. Furthermore, the thermal sensitivity of F127-shell MNPs also was measured by controlled-temperature UV-Vis spectra, PL, and DLS.
4. The unique feature of our novel drug carriers is that it is possible to load amphoteric drug (or a combination of drug) that can partition into the F127 shell surrounding iron oxide nanoparticles.
5. The actuating mechanism of this-type drug carrier is used the hyperthermia to arise temperature. When the arising temperature is higher than CMT or LCST, the drugs can be burst from the dual-functional drug carriers by the volume compressed.
6. By an external oscillating MF, the heat source can be produced to induce the instantaneous drug delivery by sharply volume transition (10-fold) from 15oC to 35oC, which is approximately 5 times higher at first 5-min than that just by incubation at 35oC water bath.
7. This bursting drug delivery is very important to tumor and some emergency
therapy. In addition, the F127-shell MNPs can produce heat by hyperthermia, which not only provides thermal response on the F127 shell, but also kills the tumor cell when the temperature rises above 40°C.
8. Therefore, the dual functional magnetic drug carriers offer a promising technology for “switchable” drug release in the biomedical studies by using an external magnetic field.
9. However, it would be better if CMT of F127-MNPs can be raised to 40oC, because it is more suitable and potential for human body, which means it will release drug at 40oC but stop at 37oC.
10. It is in the progress in our group to synthesize the Pluronic series by covalently bonding with hydrophilic compounds in order to achieve the higher CMT. In other words, it is also possible to functionalize our F127-shell MNPs with ligand or antibodies to further enhance their potential, including as agents (ex. quantum dots) for magnetic imaging or tracking.
11. The single and double layer of activated Pluronic® nanocapsules (F127-NPC and F68-NPC) were prepared by single and double mulsification/solvent evaporation method, respectively, and then cross-linked by gelatin and EDC (two-step cross-linking).
12. The dual-functional (magnetic/thermal) drug carriers (F68-EDC-IO) were successfully fabricated by in-situ precipitate and self-assembly processes, and the characterization was examined by TEM and XRD analysis. The iron oxide nanoparticle encapsulated into the nanocapsules was tentatively assigned to iron carbonyl (C9Fe2O9) and displays nanocrystal characterization.
13. Controlling the concentration of Pluronic® could fabricate different size micelles (as a tank to incubate the iron oxide nanoparticles) and thus clould dominat the size of iron oxide nanoparticles (The lower concentration Pluronic® F68-NPC, the larger particle size and stronger crystallization of iron oxide nanoparticle are).
14. All of nanocapsules exhibited thermo response behavior (CMT of F127-series:
22-26oC; CMT of F68-series: 39-43oC), and CMT measured by DLS would obviously decrease after activated by NPC and slightly increase after gelatin
cross-linking. Moreover, CMT was almost no obvious change after EDC cross-linked and iron oxide nanoparticles encapsulated. F68-series nanocapsules were more suitable and potential to use in the body, because the CMT is above body temperature
15. For the natural drug release, all of nanocapsules display stable release in the range of 4 and 37oC and the drug release rate would increase gradually with temperature rising (4-37oC), but the rate of release accelerates fast at 45oC (above CMT). The increase of release rate may be attributed to the volume-shrinkage of nanocapsules.
16. By an external oscillating MF, the heat source can be produced to induce the instantaneous drug delivery by sharply volume transition (ca. 10-fold) from 20oC to 45oC, accompanying the enlarged and cracked pore by magnetic vibration of iron oxide nanoparticle, which is approximately 20 times higher at first 10-min operation than that just by incubation at 45oC water bath. This squeezing drug delivery is very important to apply in tumor and some emergency therapy.
17. Heat can produce by hyperthermia in the sample F68-EDC-IO nanocapsules, which not only provides thermal response on the Pluronic® shell, but also kills the tumor cell when the temperature rises above 40°C. Therefore, the dual functional magnetic drug carriers offer a promising technology for “switchable” drug release in the biomedical studies by using an external magnetic field. The novel “smart”
biomaterials promise numerous potential applications in externally actuated drug delivery systems for release of drug molecules, such as tumor and epilepsy therap.
18. In summary, the dual-responsive (magnetic/thermal) materials can be anticipated for a much promising drug-delivery systems and can enhance the practicability of thermo-sensitive hydrogels.
19. The magnetic nanoparticles still provides some advantages, such as grafted probe-protein onto magnetic nanoparticles for “target” drug delivery systems and using magnetic resonance image (MRI) techniques for cell-tracking, as well as the magnetic materials can be “recycle” used and separating cells by magnet catching. Therefore, according to combine these techniques with thermo-sensitive
ferrogel, it is easy to find the region of disease, and delivers drug in the accuracy region by magnetic fields controlled (hyperthermia).
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