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Preparation and evaluation of novel self-assembled apo-transferrin-stearic acid nanoparticles in cancer targeting
- Alternative Title
- Preparation and evaluation of novel self-assembled apo-transferrin-stearic acid nanoparticles in cancer targeting
- Author(s)
- AMIN HARDIK HASTIBHAI
- Alternative Author(s)
- AMIN HARDIK HASTIBHAI
- Advisor
- Beom-Jin Lee
- Department
- 일반대학원 약학
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2017-08
- Language
- eng
- Keyword
- transferrin; nanoparticle; self-assembly; paclitaxel; doxorubicin
- Alternative Abstract
- The major hurdle in cancer treatment is to precisely target drugs at cancer site. Transferrin-Transferrin receptor interaction is widely exploited to target cancer cells due to over-expression of transferrin receptor by many cancer cells. In this study, novel apo-transferrin-stearic acid (TfS) conjugates were prepared and characterized by FTIR, MALDI-TOF mass spectroscopy and TNBS assay to confirm their structure. The prepared TfS conjugates showed self-assembly in water and formed nanoparticle which were evaluated by SEM, TEM, particle size and zeta potential analysis. Doxorubicin HCl was adsorbed on surface of NP by incubation method and prepared doxorubicin containing TfS NP (NP+DOX) were analyzed for their cell targeting and cell killing properties in transferrin receptor over-expressing cell lines A549 and HCT116 cells by MTT assay, confocal microscopy and fluorescent assisted cell sorting flow cytometry. The data showed that NP+DOX exhibited improved targeting and cell killing effects compared to doxorubicin. The cell killing efficiency of NP+DOX was similar, to that of Doxil with improved cell uptake as seen from confocal microscopy. The prepared drug delivery system has potential to target transferrin receptor over-expressing cancer cells and prevents possible off-target effects. In this study, paclitaxel was encapsulated in self assembled apo-transferrin-stearic acid nanoparticles and the prepared nanoparticles were evaluated for their transferrin receptor targeting and cell killing effects. The nanoparticles exhibited spherical smooth surface in SEM and TEM studies. The particle size of paclitaxel loaded nanoparticle was 326.97 ± 2.03 nm with loading and encapsulation efficiency being 7.94 ± 1.60 and 71.10±4.12. Paclitaxel loaded nanoparticle showed 7 fold reduction in LC50 in breast carcinoma cells MCF-7 compared to that of free paclitaxel, accounting for increased cytotoxicity due to effective targeting of cells. Confocal study confirmed this observation as uptake of nanoparticle was inhibited in presence of transferrin receptor blocking treatment. Flow cytometry data also confirmed above observations depicting time dependent uptake of nanoparticles and reduction in uptake in case of receptor blocking. These data suggest for advantage of developed drug delivery platform in cancer cell targeting and subsequently cell killing effect.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Pharmacy > 4. Theses(Ph.D)
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