Enzymatic Synthesis of Functional PEGylated Adipate Copolymers

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Many new active pharmaceutical ingredients (APIs) exhibit poor water solubility, hindering their therapeutic application.
• Polymeric nanoparticles (NPs) are widely used for encapsulating hydrophobic APIs, with polyethylene glycol (PEG) being a common choice due to its biocompatibility and ability to extend drug residence time.
• However, PEGylation faces challenges including immunogenicity, limited biodegradability, and restricted chemical functionality.

Purpose of the Study:

• To develop novel PEGylated polyesters using an enzymatic synthetic route.
• To investigate the influence of incorporating hydrophobic diols into the PEGylated backbone on NP formation, stability, and drug encapsulation.
• To identify optimal formulations for enhanced drug delivery of hydrophobic APIs.

Main Methods:

• Enzymatic synthesis of novel PEGylated polyesters.
• Incorporation of hydrophobic diols (1,6-hexanediol and 2-hydroxyethyl disulfide) into the PEGylated backbone at a 50:50 ratio.
• Characterization of nanoparticle (NP) formation, stability, biocompatibility, and encapsulation efficiency.

Main Results:

• Two formulations, PEGA-Hex 50% (PEG and 1,6-hexanediol) and PEGA-SS 50% (PEG and 2-hydroxyethyl disulfide), emerged as the most promising candidates.
• These selected formulations demonstrated adequate NP stability and biocompatibility.
• Superior encapsulation efficiency was observed for PEGA-Hex 50% and PEGA-SS 50% compared to other variants.

Conclusions:

• Novel PEGylated polyesters synthesized via an enzymatic route offer a viable strategy for delivering hydrophobic APIs.
• The incorporation of specific hydrophobic diols significantly enhances NP stability and drug encapsulation efficiency.
• PEGA-Hex 50% and PEGA-SS 50% represent promising candidates for developing advanced drug delivery systems for challenging APIs.