Dendrimers are nanosized, non-immunogenic, hyperbranched polymeric systems. Dendrimer synthesis can be precisely controlled in size, shape, molecular mass, composition, and reactivity. Two generations of positively charged poly (amidoamine) dendrimers (PAMAMs) were selected for the study as potential carriers for 5-fluorouracil (5FU), a drug primarily used in treating colorectal cancer. Analytical techniques such as UV-Vis and NMR spectroscopy have shown that the most critical factor determining the formation of the PAMAM-5FU complex is the starting components' protonation degree. The change in the system's protonation degree was monitored using the zeta potential measurement as a function of the system's pH and ionic strength. As a result of the dendrimer molecule interaction with the drug, a systematic decrease in charge of the complex was observed, indicating the dendrimer molecule's charge compensation. However, these measurements do not provide precise information about the location of 5FU molecules in dendrimers' structure. The observed shifts in the H<sup>1</sup> NMR spectrum indicate drug molecules' presence inside dendrimers' structure and on its surface.<br/>Additionally, using the QCM-D method, the adsorption efficiency, and the number of drug molecules immobilized in the dendrimer structure was determined. The tests confirmed the system's ability to attach about 20 5FU molecules per one dendrimer molecule for the fourth generation dendrimer and approximately 25 molecules for the sixth generation dendrimer. Comparing these values with the nominal number of amine groups present in the dendrimer structure, a system yield of 16% for G4PAMAM and 5% for G6PAMAM dendrimers was obtained. These results correlate well with the spectroscopic studies.<br/>Cytotoxicity studies (MTT and MTS tests) show no effect of dendrimers against mouse fibroblast cells (L929) and regular activity of the PAMAM-5FU complex against five human cell lines: malignant melanoma (A375), ovarian cancer (MDAH), glioma (SNB-19 ), prostate cancer (Du-145) and colon adenocarcinoma (HT-29).

PAMAM dendrimers as nanocarriers for 5-fluorouracil: effectiveness of complex formation and cytotoxicity studies

ACS Spring Meeting 2021

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