**2. Results**

#### *2.1. Synthesis and Characterization of Poly(Glycerol Sebacate)*

PGS was synthesized via a polycondensation reaction between glycerol and sebacic acid to first form a linear aliphatic polyester (Scheme 1a) that can be further cured to yield a crosslinked thermoset elastomer (Scheme 1b).

**Scheme 1.** Synthesis of PGS. (**a**) synthesis of linear PGS through polycondensation of glycerol and sebacic acid. (**b**) curing reaction to yield a thermoset.

The main hurdle in the synthesis of PGS derives from the nature of the monomers. While glycerol can be described as an A3 type monomer, sebacic acid is a difunctional species that can be described as a B2 type monomer. This difference in the number of reactive functionalities between the two molecules results in difficulties in proper control of the reactivity during the polycondensation reaction. In this regard, even if it is true that the primary alcohol groups in glycerin are more reactive than the secondary ones, a non-proper management of the reaction conditions can result in the formation of an undesired crosslinked material. Literature reports on the synthesis of PGS usually rely on an equimolar mixture of the two monomers, to target a linear polyester. The reaction is carried out for very long times at low temperatures, in order to limit the occurrence of crosslinking [29]. During this step, the molecular weight of the linear segments has limited control through different reaction times. After this first condensation step, the crosslinking reaction is carried out to yield a thermoset. The mechanical properties of the crosslinked product can be controlled through the curing conditions that can give access to a significant amount of different products with different properties [30].

This classical procedure for the synthesis of PGS requires long times, lasting several days. On the contrary, the procedure reported in this paper is based on a different approach. The two monomers are loaded in different molar amounts, with an excess of sebacic acid to partially make up for the excess of alcoholic functionalities. The reaction was carried out for 6 h at 170 ◦C resulting in a linear polymer in the form of a waxy solid that was further employed for the preparation of nanoparticles.

PGS was characterized through size exclusion chromatography (SEC) for the determination of the molecular weight and polydispersity. Molecular weight data of the polymer were detected as follows: (Mn) = 3100 Da; (Mw) = 12,000 Da; D = 4.0, expressed as polystyrene equivalents. The high polydispersity of the polymer was attributed to the occurrence of branching reactions. These kinds of reactions are competitive with a linear chain growth and affect the microstructure of the product resulting in a complex mixture of species. However, the product was filtered before the analysis in order to eliminate every possible crosslinked fraction.

DSC analysis pointed out the semicrystalline nature of the polymer, with Tg = −11.3 ◦C; Tm = 8.1 ◦C.

NMR and FT-IR were also carried out in order to depict the structural features of the polymer. Spectral data were in good agreement with the literature [31]. Spectra are shown in the supporting information.
