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 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 complement system, showing at the same time only a restrained effect on blood coagulation. Moreover, the new copolymer was biodegradable and had low cytotoxicity, before and after degradation, which was demonstrated with different cell lines. In the second project, the biodegradable hPG-co-PCL was used as macroinitiator for the synthesis of pH responsive nanocarrier for the treatment of pancreatic cancer. It is well established that, while the human body generally presents a neutral pH, the cancer is characterized by a local acidic pH. This feature can be employed to induce the release of the guest molecules only at the desired site of action. The hPG-co-PCL core was used to graft a polycarbonate block, which was further functionalized with a tertiary amine, namely, N,N’-dibutylethylene diamine. The new polymer was used both for the covalent conjugation and physical encapsulation of the anticance drug gemcitabine (GEM). The nanocarrier was able to deliver its cargo in a pH-dependent fashion, with different rates depending on the type of loading. In the third project, the upscaling of the synthesis of hPG-co-PCL and its employment as a nanocarrier for hydrophobic guests, both before and after sulfation, was investigated. The parameters, which govern the synthesis of the hPG-co-PCL, were inspected to determine the conditions that lead to different molecular weights while improving the gram scale of the product. The production on large scale at low costs is a primary need to access the market. Moreover, the relationship between tumor and inflammation is generally accepted. The dPGS has already demonstrated to be capable of targeting the tumoral environment, which suggests using new abovementioned nanocarriers for the delivery of anticancer drugs. Two possible guests were physically encapsulated in the biodegradable copolymers: the anticancer drug doxorubicin, and a near infrared (NIR) dye. A great interaction both with doxorubicin and the dye was observed. The sulfated compounds displayed the best capacity of delivering the guest to the tumor cell line Hela in vitro, with increased performance depending on the molecular weight and correlating loading capacity. Moreover, the best candidate for the delivery of doxorubicin was loaded with the hydrophobic NIR dye S 0796 and tested in vivo to explore the capacity of the polymer in targeting the tumor. Accumulation in the tumor was observed 24 h after the injection, confirming the affinity of the sulfated compound to inflamed and cancerous tissue. These preliminary results show the potential for the employment of the new biodegradable sulfated nanocarriers for tumor therapy. These outcomes describe the potential of the new nanocarriers for biomedical application, but further studies are needed to expand these findings. In vivo studies, which demonstrate the stability of the nanocarriers in the blood stream and a sufficient circulation time, would be necessary to confirm their suitability as nanocarriers. Due to the large diversity of anticancer drugs, a screening of the possible guests should be performed to determine which cancer type represents an appropriate target for the above-presented nanocarriers. The increase in the hydrophobic caprolactone component might be taken in account to ensure a better loading capacity of small molecules like dexamethasone. The influence of the encapsulation method, namely the conjugation in comparison to the physical entrapment, of both the anticancer drugs and NIR dye should be studied to understand its role on the drug delivery in vivo. Moreover, the possibility to use the new biodegradable carriers for theranostics applications shall be further explored.
