Heterofunctionalized polyphenolic dendrimers decorated with caffeic acid: Synthesis, characterization and antioxidant activity

Dendrimers, branched polymer structures, have been widely studied as efficient drug carriers. Scientists are trying to find new dendrimer-based formulations with the properties needed for biomedical applications such as improved bioavailability, low toxicity and high transfection profiles. The unique drug delivery properties of carbosilane dendrimers have already been demonstrated. Their efficacy has been further improved by conju-gation with polyphenols, plant secondary metabolites with a wide range of biological activities, including antioxidant effects that are beneficial for human health. The present study focuses on synthesis and character-ization of two new types of carbosilane dendritic systems, one family presents one or two caffeic acid units and ammonium groups on the surface to make them water soluble. The other family has, in addition to the two mentioned functionalities, one or two polyethylene glycol (PEG) chains in the structure to increase the biocompatibility of the system. Carbosilane dendrimers with caffeic acid have low toxicity and protect eryth-rocytes against oxidative hemolysis. These dendrimers also decrease AAPH-induced ROS production in human fibroblasts.Various techniques demonstrating such antioxidant activities have been applied in the current research. The best antioxidant properties were shown for the dendrimer with two PEG-caffeic acid moieties. Further aspects of the biochemical characterization of the dendrimers are also considered and discussed.Ministerio de Ciencia e InnovaciónMinisterio de Economía y CompetitividadJunta de Comunidades de Castilla-La ManchaComunidad de MadridPolish National Agency for Academic Exchang

Lipid-coated ruthenium dendrimer conjugated with doxorubicin in anti-cancer drug delivery: Introducing protocols

One of the major limitations for the treatment of many diseases is an inability of drugs to cross the cell membrane barrier. Different kinds of carriers are being investigated to improve drug bioavailability. Among them, lipid or polymer-based systems are of special interest due to their biocompatibility. In our study, we combined dendritic and liposomal carriers and analysed the biochemical and biophysical properties of these formulations. Two preparation methods of Liposomal Locked-in Dendrimers (LLDs) systems have been established and compared. Carbosilane ruthenium metallodendrimer was complexed with an anti-cancer drug (doxorubicin) and locked in a liposomal structure, using both techniques. The LLDs systems formed by hydrophilic locking had more efficient transfection profiles and interacted with the erythrocyte membrane better than systems using the hydrophobic method. The results indicate these systems have improved transfection properties when compared to noncomplexed components. The coating of dendrimers with lipids significantly reduced their hemotoxicity and cytotoxicity. The nanometric size, low polydispersity index and reduced positive zeta potential of such complexes made them attractive for future application in drug delivery. The formulations prepared by the hydrophobic locking protocol were not effective and will not be considered furthermore as prospective drug delivery systems. In contrast, the formulations formed by the hydrophilic loading method have shown promising results where the cytotoxicity of LLD systems with doxorubicin was more effective against cancer than normal cells