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RSS FeedsIJMS, Vol. 22, Pages 11167: Poly(amidoamine) Dendrimers as Nanocarriers for 5-Fluorouracil: Effectiveness of Complex Formation and Cytotoxicity Studies (International Journal of Molecular Sciences)

 
 

16 october 2021 11:19:51

 
IJMS, Vol. 22, Pages 11167: Poly(amidoamine) Dendrimers as Nanocarriers for 5-Fluorouracil: Effectiveness of Complex Formation and Cytotoxicity Studies (International Journal of Molecular Sciences)
 


Two generations of positively charged poly(amidoamine) dendrimers (PAMAMs) were selected for study as potential carriers for the anticancer drug 5-fluorouracil (5FU), a drug primarily used in the treatment of colorectal cancer. Analytical techniques, such as UV-Vis spectrophotometry, NMR Spectroscopy and Laser Doppler Velocimetry (LDV), have shown that the most critical factor determining the formation of a PAMAM–5FU complex is the starting components` protonation degree. The tests confirmed the system`s ability to attach about 20 5FU molecules per one dendrimer molecule for the G4PAMAM dendrimer and about 25 molecules for the G6PAMAM dendrimer, which gives a system yield of 16% for the fourth generation and 5% for sixth generation dendrimers. Additionally, using the QCM-D method, the adsorption efficiency and the number of drug molecules immobilized in the dendrimer structure were determined. A new aspect in our study was the determination of the change in zeta potential (ζ) induced by the immobilization of 5FU molecules on the dendrimer`s outer shell and the importance of this effect in the direct contact of the carrier with cells. Cytotoxicity tests (resazurin reduction and MTS tests) showed no toxicity of dendrimers against mouse fibroblast cells (L929) and a significant decrease in cell viability in the case of four human malignant cell lines: malignant melanoma (A375), glioblastoma (SNB-19), prostate cancer (Du-145) and colon adenocarcinoma (HT-29) during incubation with PAMAM–5FU complexes. The purpose of our work was to investigate the correlation between the physicochemical properties of the carrier and active substance and the system efficiency and optimizing conditions for the formation of an efficient system based on PAMAM dendrimers as nanocarriers for 5-fluorouracil. An additional aspect was to identify potential application properties of the complexes, as demonstrated by cytotoxicity tests.


 
66 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 22, Pages 11168: Long Non-Coding RNA ANRIL as a Potential Biomarker of Chemosensitivity and Clinical Outcomes in Osteosarcoma (International Journal of Molecular Sciences)
IJMS, Vol. 22, Pages 11169: Extracellular Environment-Controlled Angiogenesis, and Potential Application for Peripheral Nerve Regeneration (International Journal of Molecular Sciences)
 
 
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