Development of polysaccharide-based nano-systems containing lactoferrin for treatment of respiratory infections

Viral respiratory infections affect people of all ages, the emergence of new viruses and the selection of drug-resistant viral strains have prompted the development of new therapeutic strategies. The advent of nanotechnology in biomedicine has opened the way to new therapies for the delivery of drugs, proteins and nucleic acids. The small size provides these systems with excellent chemical-physical and pharmacokinetic properties, making it possible for them to transit inside small capillaries and cross biological barriers [1]. Among nano-carriers, the most promising in the biomedical field are those based on polysaccharides thanks to their biodegradability, bioactivity and biocompatibility as well as the presence of many functional groups that can be used to improve drug loading. This work was aimed at developing innovative therapies for the treatment of infection by respiratory viruses, such as influenza virus and adenovirus, and of the inflammatory processes caused by them. Lactoferrin (Lf) possesses many biological functions including antimicrobial, antitumor, anti-inflammatory activities [2]. Many studies have shown protective effects of lactoferrin against common viral infections [3]. Polysaccharide-based nanocarriers were developed in order to improve the lactoferrin therapeutic index. Alginate and hyaluronic acid were used to prepare two different nano-complexes for protein delivery using the complex coacervation method. The obtained systems were characterized by DLS technique to investigate their dimensions, polydispersity and stability. Morphological analysis, performed by scanning electron microscopy (SEM), confirmed the presence of nanostructures while thermal analysis (TGA) evidenced the formation of polysaccharide-protein interactions with an improvement in thermal stability (increase in TD) of the nanocomplexes as protein concentration increased. Circular dichroism measurements displayed no conformational change of lactoferrin after sonication treatment or interaction with alginate and hyaluronic acid. By physicochemical characterization were identified the most promising complexes then subjected to cytotoxicity analysis by MTT test on two different cell lines (A549 and MDCK). Preliminary results were positive. Further tests are ongoing to evaluate the anti-inflammatory and antiviral activity of the nanocomplexes.