Biodegradable Sulfated Dendritic Nanocarriers for Biomedical Applications [thesis]

Magda Ferraro, Universitätsbibliothek Der FU Berlin
2020
The increasing need to provide more efficient delivery of drugs for different illnesses is a key topic in the biomedical field. Synthetic polymers find wide employment in the development of diverse tools that perform their activity on the disease or can help to deliver small molecules like drugs to the desired site of action. In this thesis, biodegradable polyglycerol-based polymers for the treatment of inflammatory diseases and the delivery of hydrophobic guests were presented. Hyperbranched
more » ... ed. Hyperbranched polyglycerol, which is a highly biocompatible polymer, with easy synthesis, hydrophilic character, and numerous end groups suitable for further functionalization, was chosen to develop new biodegradable compounds. The copolymerization of glycidol with Ɛ-caprolactone resulted in a biodegradable version of the well-established hyperbranched polyglycerol (hPG), thanks to the presence of ester bonds in the backbone. The copolymer has been further functionalized, characterized, and studied invitro regarding its biocompatibility, biodegradability, and suitability for the application in the biomedical field. In the first project, this new copolymer was functionalized to obtain a biodegradable sulfated derivate ((hPG-co-PCL)S), which has been investigated for possible applications in the treatment of inflammatory states. Previous studies have highlighted the high affinity of dendritic polyglycerol sulfate (dPGS) to L-selectin but also demonstrated its accumulation in organs such as the spleen and liver, remarking the necessity of biodegradable compounds for in vivo applications. In this work, it was observed that the biodegradable version of dPGS is a valid alternative to the well-established one and, depending on the molecular weight and the degree of sulfation, it was possible to achieve diverse performance profiles concerning the inhibition of the binding of L-selectin towards its ligands, a crucial step in the recruitment of leukocytes to the site of inflammation. The (hPG-co-PCL)S was also capable to reduce the activity of the [...]
doi:10.17169/refubium-26972 fatcat:6xz5vuhpd5foddlhygrqf4o7pq