Biodegradable hyperbranched polyglycerol with ester linkages for drug delivery

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Nanotechnology

Background:

• Biodegradable polymers are crucial for developing advanced drug delivery systems.
• Hyperbranched polyglycerols (dHPGs) offer unique structural properties for biomedical applications.
• Developing biocompatible and effective carriers for anticancer drugs remains a significant challenge.

Purpose of the Study:

• To synthesize biodegradable hyperbranched polyglycerols (dHPGs) via hybrid polymerization.
• To functionalize dHPGs for drug conjugation and evaluate their properties as a drug delivery system.
• To assess the biodegradability, cytotoxicity, drug release kinetics, cellular uptake, and anticancer efficacy of the dHPG-based system.

Main Methods:

• Synthesis of dHPGs using oxyanionic initiating hybrid polymerization of glycerol and glycidyl methacrylate.
• Conjugation of methotrexate (anticancer drug) and Rhodamine-123 (fluorescent probe) onto dHPGs.
• Characterization of dHPG-drug conjugates, including micelle formation and drug release studies at different pH values.
• In vitro evaluation of cellular uptake and cytotoxicity assays (MTT) against cancer cells.

Main Results:

• Successfully synthesized dHPGs with ester linkages, demonstrating good biodegradability and low cytotoxicity.
• Developed amphiphilic dHPG-methotrexate (dHPG-MTX) conjugates forming micelles in aqueous solutions.
• Observed faster methotrexate release at pH 5.0 compared to pH 7.4, indicating pH-responsive drug delivery.
• Demonstrated efficient internalization of dHPG-MTX micelles by cancer cells and high anticancer efficacy via MTT assay.

Conclusions:

• Biodegradable hyperbranched polyglycerols (dHPGs) are promising materials for developing effective and safe drug delivery systems.
• The dHPG platform allows for easy conjugation of therapeutic agents and exhibits desirable properties like biodegradability and low cytotoxicity.
• The pH-responsive, micelle-forming dHPG-MTX system shows significant potential for targeted cancer therapy.