In this study we employed self-designed PDLLA-PEG-PDLLA (PLEL) thermosensitive
hydrogel to blend with
norcantharidin (NCTD), a hydrophilic chemotherapeutic drug possessing curative effect on primary
hepatocellular carcinoma (HCC) and adverse effects, then utilized the composite in HCC interstitial
chemotherapy. PLEL copolymer was synthesized by ring-opening polymerization, NCTD-loaded PLEL
hydrogel was prepared in a simple and reasonable way. The addition of NCTD had no significant effect on the temperature-dependent rheological properties of PLEL
hydrogel. The pH values of NCTD-loaded gel solutions (13 wt%) and free NCTD solutions with three drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL under different storage conditions met the pH requirement of small-volume injection. There was no significant difference among the drug release behaviors of NCTD-loaded
gels with drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL, they fitted first-order dynamics, exhibited significantly slower drug release than free drug solutions and the release was mainly based on drug diffusion. Drug-loaded gel
solution (13 wt%) could evenly distribute throughout
tumor tissue before converting into gel after being intratumorally injected and was able to significantly prolong retention time of the drug in
tumor compared to free drug
solution. The sustained-release performance of NCTD-loaded gel (13 wt%) was confirmed from the perspective of pharmacodynamics in vitro. The in vivo evaluation demonstrated that intratumoral injection of NCTD-loaded PLEL gel (13 wt%) was capable of improving curative effect of the drug and reducing its toxicity.