Intratumoral delivery of chemotherapeutic agents may permit the localization of drugs in
tumors, decrease nonspecific targeting and increase efficacy. The pH-responsive
peptide hydrogel is considered a suitable carrier for chemotherapeutics via intratumoral injection. Thus, a study was carried out to develop a
paclitaxel (PTX) drug delivery system using a pH-responsive FER-8
peptide hydrogel for
tumor targeting. The pH-sensitive
hydrogel system was characterized for loading capacity,
acid sensitivity, structure, rheology, morphology, drug release, in vitro cytotoxicity and in vivo efficacy in H22
tumor-bearing mice. The stable FER-8
peptide hydrogel with high drug-loading capacity was formed at pH 7.4 by the self-assembly of
peptide, whereas higher degradation was observed at an acidic pH. Circular dichroism and rheology confirmed the suitable meshwork structure and enhanced mechanical properties of the
hydrogel. The FER-8
peptide hydrogel fibers were found to have an average size less than 500 nm at pH 7.4, which was confirmed by TEM and DLS analysis. Sustained release of PTX at pH 5.5 was observed for the FER-8
peptide hydrogel (HG-PTX) for almost 1 week. In vitro cytotoxicity studies indicated that the FER-8
peptide hydrogel increased the drug accumulation in HepG2 cells and effectively inhibited the growth of HepG2
tumor cells compared with free drugs. Furthermore, in vivo studies using H22-bearing mice indicated that the
paclitaxel-loaded FER-8
peptide hydrogel significantly increased the amount of drugs in
tumor tissues and showed prolonged retention (96 hours) at the
tumor site by intratumoral injection. The in vivo anti-
tumor studies confirmed the pH-sensitive properties of HG-PTX, which allowed the drug to be triggered by the acidic pH environment at
tumor sites, provided sustained delivery of the drug and enhanced
tumor inhibition. In conclusion, HG-PTX provides an attractive strategy and potential vehicle for efficient anti-
cancer drug delivery. The carrier can enhance
tumor targeting, prolong retention, reduce systemic side effects and increase the accumulation of drugs at the
tumor site.