Hydrogen bonding-enhanced micelle assemblies for drug delivery

Area of Science:

• Polymer Chemistry
• Materials Science
• Biomedical Engineering

Background:

• Ring-opening polymerization (ROP) enables the synthesis of functionalized block copolymers.
• Cyclic carbonates derived from 2,2-bis(methylol)propionic acid (bis-MPA) can incorporate hydrogen-bonding urea groups.
• These urea groups offer potential for supramolecular assembly in drug delivery systems.

Purpose of the Study:

• To synthesize and characterize poly(ethylene glycol)-block-poly(ethyl-random-urea carbonate) (PEG-P(E(1-x)-U(x))C) block copolymers.
• To investigate the effect of urea functionalities on micelle formation, stability, and drug loading capacity.
• To evaluate the in vitro drug release profile and cytotoxicity of the developed drug delivery systems.

Main Methods:

• Synthesis of functionalized cyclic carbonates via ROP.
• Preparation of PEG-P(E(1-x)-U(x))C block copolymers.
• Characterization of micelle formation, critical micelle concentration (cmc), and particle size.
• In vitro drug loading and release studies with doxorubicin (Dox).
• Cytotoxicity assays using HEK293 and HepG2 cell lines.

Main Results:

• Urea-functionalized block copolymers exhibited significantly lower cmc and improved kinetic stability compared to conventional PEG-PTMC copolymers.
• Dox loading into urea-bearing micelles was improved, and the undesirable increase in micelle size upon drug incorporation was mitigated.
• In vitro drug release showed a slight decrease in Dox release rate with increasing urea content.
• The block copolymers demonstrated no significant cytotoxicity, while Dox-loaded micelles effectively targeted HepG2 cancer cells.

Conclusions:

• The incorporation of H-bonding urea groups into PEG-based block copolymers is a promising strategy for developing robust supramolecular drug delivery systems.
• These novel materials offer enhanced micellar stability and drug loading, addressing key challenges in doxorubicin delivery.
• The developed block copolymers show potential for effective and safe cancer therapy applications.