Formation of dendrimer-guest complexes as a strategy to increase the solubility of a phenazine N, N′-dioxide derivative with antitumor activity

Abstract

Poly(amidoamine) and Poly(propylenimine) dendrimers with different generations and peripheral groups were studied as solubility enhancers and nanocarriers for 7-bromo-2-hydroxy-phenazine N 5 , N 10 -dioxide. This compound possesses potential antitumoral and anti-trypanosomal activity, but its low solubility in physiological media precludes its possible application as therapeutic drug. The amino terminated dendrimers association with the active compounds as observed trough NMR studies showed that electrostatic interactions are essential in the solubilization enhancement process. The obtaining of a stable and no cytotoxic formulation makes the drug-carried association a suitable strategy for the generation of a drug delivery system for phenazine derivatives.

Functionalized PVA film with good adsorption capacity for anionic dye

“…Generally, the NMR results resembled, to some extent, those reported in previous studies. [42,45] Additionally, the number average molecular weight ( ¯Mn ) and polydispersity index PDI ( ¯Mw / ¯Mn ) of the prepared PAMAM were determined via GPC as 3472 g/mole and 1.03, respectively.…”

Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

“…If the metabolization is by reduction of the N- oxide to amines, via two electrons, it leads to an agent that could interact with biomolecules like DNA, RNA polymerases and topoisomerases or both and the amine-protonation promotes an exclusively confined in the diseased tissue due to the acidic pH of the tumor cell microenvironment in the hypoxic conditions [ 13 , 14 ]. Derivatives of phenazine dioxides, such as the compound 2-amino-7-fluorophenazine 5,10-dioxide (FNZ), have low aqueous solubility (208 µg/mL) that prevents their selective action at the tumor level, their oral administration, parenteral and transdermal [ 11 , 15 , 16 ]. Thus, its clinical use would be restricted, due to the low biodistribution of the body aqueous milieu.…”

“…Fortunately, nanomedicine has emerged as a tool for solving solubility problems [ 16 ]. This discipline involved the development of systems, known as nanosystems, carriers or vehicles, that additionally allow passive transport to the tumor microenvironment, due to inconsistent blood vessels (diameter, irregular shape, abnormal protrusions and blind ends), absence of supporting tissues of the vasculature, vascular hyperpermeability, fenestrations of 100 nm to 2 µm in diameter, poor lymphatic system and a thermodynamically favorable environment in terms of retention of nanoparticles, as long as they are smaller than endothelial “hollow” pores.…”

A comparative study on solubility improvement of tetracycline and dexamethasone by poly(propylene imine) and polyamidoamine dendrimers: An insight into cytotoxicity and cell proliferation

“…However, drug molecules interact with tertiary amine and amide groups of dendrimers via hydrogen bonding (Devarakonda et al, ; Szymański et al, ). PAMAM dendrimers have amide groups beside tertiary amines which helped better improvement of solubility comparing to PPI dendrimers (Dib et al, ). Also, G4.0 PAMAM had higher number of cationic terminal groups with respect to G3.0 PAMAM that caused better opportunity for more electrostatic interactions with the negatively‐charged drug molecules and better improvement of drug solubility.…”