Cationic, Lipidic, and Hybrid Amino- and Guanidinoglycoside Conjugates. Synthesis, Antibacterial Activity and Cellular Uptake of New non-Viral Vectors for Gene and Drug Delivery

      Аннотация: In recent years new non-viral vectors for gene and drug delivery have become more and more important in order to overcome the use of viral vectors, due to their potential dangerous drawbacks, and facilitate drug entery into cells. Aminoglycosides with guanidinoglycosides, their derivatives, are a large family of well-known potent antibiotics. The objetive of this work was the use of aminoglycosides for the development of: new multifunctional gene delivery vectors, new multivalent carriers for drug delivery and a small collection of new antibiotics. So, different kind of non-viral vectors for gene delivery studies were synthesized, using dendrimeric, lipidic and hybrid lipidic-dendrimeric cationic systems grafted with aminoglycosides. Furthermore interesting conjugates for drug delivery studies, were prepared grafting PAMAM dendrimers with guanidinoglycosides due to their great ability to promote the cellular uptake of macromolecules at namolar concentration in a heparan sulphare dependent way. Finally, the chemistry of aminoglycosides was investigated with an innovative multicomponent domino process to synthesize sugar-neomycin conjugates, as novel antibiotics.

Ключевые слова: Drug delivery, Aminoglycosides, Guanidinoglycosides, PAMAM, Gene Delivery, Antibacterial Activity, Antibiotics, Lipidic Carriers, Cationic Carriers, Cellular Upteke, Mechanism of Internalization