Tunable temperature-responsive supramolecular hydrogels formed by prodrugs as a codelivery system

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Camptothecin (CPT) is a potent anticancer drug with strong hydrophobicity.
• Poly(ethylene glycol) (PEG) is a versatile polymer used in drug delivery.
• 5-fluorouracil (5-FU) is a water-soluble chemotherapy agent often combined with CPT.

Purpose of the Study:

• To create an amphiphilic prodrug by conjugating CPT to PEG chains.
• To develop a stable, supramolecular hydrogel system for co-delivering CPT and 5-FU.
• To investigate the temperature-responsive, reversible gel-sol transition properties of the hydrogel for controlled drug release.

Main Methods:

• Conjugation of CPT to low-molecular-weight PEG chains (500, 1000, 2000 Da).
• Formation of hydrogels via inclusion complexation with α-cyclodextrin (α-CD) and hydrophobic CPT aggregation.
• Characterization of hydrogel properties using rheology, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM).
• Evaluation of temperature-dependent controlled release profiles for CPT and 5-FU.

Main Results:

• Successfully synthesized CPT-PEG amphiphilic prodrugs.
• Formed stable hydrogels capable of loading both CPT and 5-FU.
• Demonstrated tunable, reversible gel-sol transitions controlled by PEG chain length, α-CD concentration, and temperature.
• Observed significant temperature-dependent controlled release of both drugs.
• Confirmed hydrogel structure and properties through various characterization techniques.

Conclusions:

• The developed CPT-PEG supramolecular hydrogel is a promising platform for co-delivering anticancer drugs.
• The system exhibits excellent biocompatibility and tunable temperature responsiveness for on-demand drug release.
• This hydrogel holds significant potential for advanced controlled drug delivery applications in cancer therapy.