LAUSR

Abstract Many new active pharmaceutical ingredients (APIs) demonstrate high hydrophobicity and low water‐solubility issues. In this regard, polymeric nanoparticles (NPs) have been extensively used as drug delivery carriers for the encapsulation of such APIs. One commonly used polymer is polyethylene glycol (PEG), owing to its biocompatibility, high water solubility, and capacity to prolong the drug residence time. However, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles can restrict PEG's effectiveness in physiological conditions. For this reason, in the present study, we combine the advantages offered by PEG with the use of an enzymatic synthetic route to produce novel PEGylated polyesters. Furthermore, it has been proven that incorporation of hydrophobic diols into the PEGylated backbone influences NPs formation, stability, and drug encapsulation, despite high chemical similarity. As a preliminary result, samples containing PEG and 1,6‐hexanediol in a 50 : 50 ratio (PEGA‐Hex 50 %) and PEG and 2‐hydroxyethyl disulfide in a 50 : 50 ratio (PEGA‐SS 50 %) have proved to be the most promising candidates in this small library analysed. Both samples exhibited sufficient NPs stability, biocompatibility, and superior encapsulation efficiency compared to the other variants.