Paclitaxel-loaded pH responsive hydrogel based on self-assembled peptides for tumor targeting

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Intratumoral chemotherapy offers localized drug delivery, aiming to improve efficacy and minimize off-target effects.
• pH-responsive hydrogels are promising carriers for controlled drug release, particularly in the acidic tumor microenvironment.

Purpose of the Study:

• To develop and characterize a pH-responsive FER-8 peptide hydrogel for targeted intratumoral delivery of paclitaxel (PTX).
• To evaluate the in vitro and in vivo performance of the paclitaxel-loaded hydrogel (HG-PTX) as an anti-cancer drug delivery system.

Main Methods:

• Fabrication and characterization of the FER-8 peptide hydrogel, including loading capacity, acid sensitivity, structural analysis (circular dichroism, rheology), morphology (TEM, DLS), and drug release kinetics.
• In vitro cytotoxicity assays using HepG2 cells to assess drug accumulation and tumor cell growth inhibition.
• In vivo efficacy studies in H22 tumor-bearing mice, evaluating drug distribution, retention time, and anti-tumor activity.

Main Results:

• The FER-8 peptide hydrogel demonstrated high drug-loading capacity and stability at physiological pH (7.4), with increased degradation at acidic pH (5.5).
• Sustained release of PTX from the hydrogel was observed for up to one week at pH 5.5. TEM and DLS confirmed hydrogel fiber size below 500 nm.
• In vitro studies showed enhanced drug accumulation and inhibition of HepG2 cell growth. In vivo studies confirmed prolonged drug retention (96 hours) in tumors and significant tumor inhibition in H22-bearing mice.

Conclusions:

• The paclitaxel-loaded FER-8 peptide hydrogel (HG-PTX) is a viable and effective system for targeted anti-cancer drug delivery via intratumoral injection.
• The pH-sensitive nature of the hydrogel enables triggered drug release in the acidic tumor microenvironment, enhancing therapeutic outcomes.
• HG-PTX offers a promising strategy to improve tumor targeting, prolong drug retention, reduce systemic toxicity, and increase drug accumulation at the tumor site.