Glycerol- and diglycerol-based polyesters: Evaluation of backbone alterations upon nano-formulation performance

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Polyethylene glycol (PEG)-based polyesters, while successful in biomedical applications, face challenges due to immunogenicity and poor biodegradability.
• Limitations of PEGylated polyesters include restricted chemical modification options and hydrophobicity, hindering performance in physiological conditions.
• There is a growing need for effective, biocompatible, and biodegradable alternatives to PEG for drug delivery systems.

Purpose of the Study:

• To investigate the incorporation of 1,6-hexanediol (Hex) into poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) polyesters.
• To evaluate how varying (di)glycerol:Hex ratios impact nanoparticle (NP) formation, stability, drug encapsulation, and degradation.
• To identify promising PEG-free polyester candidates for drug delivery applications.

Main Methods:

• Systematic screening of PGA and PDGA synthesized with different (di)glycerol:Hex ratios (30:70, 50:50, 70:30 mol/mol).
• Analysis of nanoparticle formation, stability in various media, and encapsulation efficiency of a model hydrophobic dye.
• Assessment of polymer degradation and in vitro/in vivo biocompatibility.

Main Results:

• Minor adjustments in polymer amphiphilicity significantly influenced NP formation, stability, drug encapsulation, and degradation.
• The PDGA-Hex 30% (70:30 diglycerol:Hex ratio) sample demonstrated comparable stability to glycerol-based counterparts.
• PDGA-Hex 30% exhibited superior encapsulation efficiency for a hydrophobic dye compared to other formulations.

Conclusions:

• Biodegradable (di)glycerol-based polyesters offer a viable and sustainable alternative to PEGylated systems for drug delivery.
• Tailoring the amphiphilicity of these polyesters through controlled monomer ratios is crucial for optimizing NP characteristics.
• The developed PDGA-Hex 30% formulation shows significant potential for advanced, PEG-free nano-systems in pharmaceutical and biomedical fields.