Tunable drug delivery using chemoselective functionalization of hydrogels

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Growing interest in cleavable linkers for controlled drug delivery.
• Hydrogels are effective for sustained drug release but struggle with small molecule diffusion.
• Limitations exist in current hydrogel systems for precise control over small molecule release.

Purpose of the Study:

• To develop functionalized polyethylene glycol (PEG) chains with pH-sensitive linkers (ester and hydrazone).
• To create microwave-assisted hydrogels using these functionalized PEG chains for controlled small hydrophilic drug delivery.
• To evaluate the drug release profiles and compare the efficacy of different linker strategies.

Main Methods:

• Functionalization of polyethylene glycol (PEG) chains with ester and hydrazone pH-sensitive linkers.
• Synthesis of microwave-assisted hydrogels incorporating these functionalized PEG chains.
• Utilizing Rhodamine B as a drug mimetic to study release kinetics.
• Assessing drug release at physiological and low basic conditions.

Main Results:

• The functionalized hydrogels demonstrated a delayed release of the drug mimetic (Rhodamine B) compared to hydrogels relying solely on steric hindrance.
• Cleavage of ester and hydrazone linkers at physiological and low basic conditions was evidenced, confirming their role in controlled release.
• The study successfully compared different release profiles, highlighting the tunability of drug release rates.
• The synthesized hydrogels show potential for modulating drug release kinetics.

Conclusions:

• pH-sensitive linkers, specifically ester and hydrazone, can be effectively incorporated into PEG-based hydrogels for controlled drug delivery.
• These functionalized hydrogels offer a tunable platform for managing the release rate of small hydrophilic drugs.
• The developed system addresses the challenge of uncontrolled diffusion of small molecules from hydrogels, paving the way for improved therapeutic applications.