Summary: | 博士 === 國立中興大學 === 材料科學與工程學系所 === 100 === In this study, the multi-functional nanoparticles containing thermosensitive polymers grafted onto the surfaces of the 6-nm monodispersed Fe3O4 magnetic nanoparticles coated by silica were synthesized using reverse microemulsions. The magnetic properties of SiO2/Fe3O4 nanoparticles show superparamagnetic behavior. Thermosensitive PNIPAM [poly(N-isopropylacrylamide)] was then grafted onto the surfaces of SiO2/Fe3O4 nanoparticles, generating thermosensitive and magnetic properties of nanocomposites. The sizes of fabricated nanoparticles with core-shell structure are controlled at about 20 nm and each nanoparticle contains only one monodispersed Fe3O4 core. For thermosensibility analysis, the phase transition temperatures of multi-functional nanoparticles measured using differential scanning calorimetry (DSC) and dynamic light scanning (DLS) were at around 35~40°C. The magnetic characteristics of these multi-functional nanoparticles were also superparamagnetic.
The loading and release of Bovine serum albumin (BSA) and vitamin D3 were also discussed. The main driving force to adsorb BSA is hydrophobic interaction between nanoparticles and BSA. Thus, at 50°C and 37°C, the polymeric shell presented as hydrophobic chains and could adsorb BSA; in contrast, the nanoparticles have no significant absorption at 25°C. Vitamin D3 loading and release behavior were also found to be dependent on the lower critical solution temperature (LCST) of the PNIPAM/SiO2/Fe3O4 nanoparticles. However, it is different to adsorption of BSA. These results show the loading vitamin D3 increases with increasing time and reaches a plateau over the 24 hours study at 25 and 37°C. At 37°C, the lower loading amount of vitamin D3 ~19.3 wt% is observed; while higher loading amount ~37.7 wt% is reached at 25°C, which is below the LCST of nanoparticles. In vitro drug release, drug squeezed out from the nanoparticles was observed when loading drug at 25°C and releasing at 37°C; nevertheless, the drug release system will undergo at physiological temperature so that loading temperature is better under the LCST.
Cytotoxicity studies were apart from two parts. The first part was conducted on Chinese hamster ovary (CHO-K1) cells and liver cancer cells (HepG2) using 3-(4,5-cimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assays revealed that cell viability of 1 mg/mL PNIPAM grafted on SiO2/Fe3O4 nanoparticles was slightly decreased after 24h incubation as compared to the lower concentration of nanoparticles. Furthermore, the concentration of 0.5 mg/mL PNIPAM grafted on SiO2/Fe3O4 nanoparticles was totally biocompatible for 48h; however, had low cytotoxicity after 72h incubation. These PNIPAM grafted on SiO2/Fe3O4 nanoparticles did not induce the morphological change in their cellularity after the exposure for 24 and 108h. The second part was observed the effect of 1,25(OH)2D3 loading of PNIPAM grafted on SiO2/Fe3O4 nanoparticles incubated with HepG2 cells. After 5 days incubation of HepG2 liver cancer cells with 1,25(OH)2D3 loading of PNIPAM grafted on SiO2/Fe3O4 nanoparticles, cell viability significant decreased that discernible from MTT and lactate dehydrogenase (LDH) assays, which is further supported by the TEM images. In conclusion, the current study demonstrated a PNIPAM grafted on SiO2/Fe3O4 nanoparticles may be used as a potential drug delivery system for controlled release.
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