Cyclodextrin Polymers As Versatile Platform For The Delivery Of Antibiotics And Antitumorals

Cyclodextrins (CyDs) are water soluble, biocompatible cyclic oligosaccharides, made of ?-D-glucopyranose units joined by ?(1-4) linkages. They received considerable attention as carriers/solubilizers for drugs thanks to their ability to host lipophilic guests in their hydrophobic cavity. Various CyD-based nanoassemblies, loading drugs via non covalent interactions have been proposed as delivery platforms and some have been considered for preclinical studies. Water soluble CyD polymers can be prepared using crosslinking method based on polycondensation in the presence of a bifunctional agent, like citric acid, or epichlorohydrin. With epichlorohydrin a CyD content up to 70% w/w can be obtained for the water soluble polymers. Most interesting, CyD polymers are able to associate drugs much more efficiently than the monomeric CyD, to enhance the aqueous solubility of several guests and to incorporate two or more drugs or therapeutic agents contemporarily. They have been considered for the delivery of antibiotics and antitumorals and for the implementation of multimodal therapy. We will report on the successful loading in a polymeric ?CyD nanoparticle (NP) of the second-line tuberculosis drug Ethionamide together with a synthetic booster using a green approach and reaching high amount of dissolved drug. The NP loading both drug and booster revealed suitable for pulmonary spray application. Next, we will discuss encapsulation of Clofazimine, a riminophenazine derivative, known as antileprosy drug. It is known to be active against a wide spectrum of Gram-positive including Mycobacteria, Staphylococci, Streptococci, Enterococci and Listeria as well as MDR resistant strains. As Clofazimine is highly lipophilic, it tends to be deposited predominantly in fat tissues. During the last decade investigations, also in the field of nanotechnology, focused on alternative routes for improved CLZ delivery. We successfully loaded CLZ in sulfobutylether ?CyD polymers using a green method and obtained promising results against Staphylococcus Epidermidis, a microbe often found in hospital context.