Effect of Ionization Degree of Poly(amidoamine) Dendrimer and 5-Fluorouracil on the Efficiency of Complex Formation—A Theoretical and Experimental Approach

Abstract

Due to their unique structure, poly(amidoamine) (PAMAM) dendrimers can bind active ingredients in two ways: inside the structure or on their surface. The location of drug molecules significantly impacts the kinetics of active substance release and the mechanism of internalization into the cell. This study focuses on the effect of the protonation degree of the G4PAMAM dendrimer and the anticancer drug 5-fluorouracil (5FU) on the efficiency of complex formation. The most favorable conditions for constructing the G4PAMAM-5FU complex are a low degree of protonation of the dendrimer molecule with the drug simultaneously present in a deprotonated form. The fluorine components in the XPS spectra confirm the formation of the stable complex. Through SAXS and DLS methods, a decrease in the dendrimer’s molecular size resulting from protonation changes at alkaline conditions was demonstrated. The gradual closure of the dendrimer structure observed at high pH values makes it difficult for the 5FU molecules to migrate to the interior of the support structure, thereby promoting drug immobilization on the surface. The 1H NMR and DOSY spectra indicate that electrostatic interactions determine the complex formation process. Through MD simulations, the localization profile and the number of 5FU molecules forming the complex were visualized on an atomic scale.

Effect of Alkaline Conditions on Forming an Effective G4.0 PAMAM Complex with Doxorubicin

“…The efficiency of DOX binding to the G4.0 PAMAM dendrimer strongly depends on the degree of ionization of the components, as in the case of 5-fluorouracil [ 35 , 36 ]. The highest efficiency occurs at pH 9.0 and 9.5, where DOX concentrations are 21 and 19 ppm, respectively.…”

“…This may be related to the tendency of DOX to aggregate strongly at high concentrations [ 28 , 37 ]. Previous studies assessed the effectiveness of forming the G4PAMAM complex with 5-fluorouracil (G4-5FU) [ 35 , 36 ]. These studies have shown that a dendrimer molecule binds around 20 5FU molecules, and the binding efficiency strongly depends on the degree of ionization of both components [ 36 ].…”

“…Previous studies assessed the effectiveness of forming the G4PAMAM complex with 5-fluorouracil (G4-5FU) [ 35 , 36 ]. These studies have shown that a dendrimer molecule binds around 20 5FU molecules, and the binding efficiency strongly depends on the degree of ionization of both components [ 36 ]. Comparing the degree of loading of both drugs (LC), the efficiency of doxorubicin is about two times higher than that of 5-fluorouracil, for which LC = 18%.…”

A high loading nanocarrier for the 5-fluorouracil anticancer drug based on chloromethylated graphene

“…It can be seen that a shoulder peak appears at 288.8 eV in the C 1s core level spectrum of 5-FU loaded CH 2 Cl-graphene, corresponding to the carbon atoms involved in C-F bonds. 56 In the Cl 2p highresolution XPS spectra of CH 2 Cl-graphene and 5-FU loaded CH 2 Cl-graphene (Fig. 7(b)), two peaks are located at 200.04 eV and 202.63 eV, which can be ascribed to Cl 2p 1/2 and Cl 2p 3/2 , respectively.…”

Poly(amidoamine) Dendrimer/Camptothecin Complex: From Synthesis to In Vitro Cancer Cell Line Studies

“…They have also been widely employed as co-delivery systems for the simultaneous administration of genes and drugs [ 11 , 12 , 13 ]. Hydrophobic drugs with different mechanisms of action and low solubility can be physically encapsulated or entrapped inside PAMAM dendrimers’ cavities or pockets [ 14 , 15 , 16 , 17 , 18 , 19 ]. This molecular encapsulation is responsible for the increased solubility in water and controlled release profile.…”