Peritoneal dissemination often occurs in advanced gastric cancer (GC) patient. However, systemic chemotherapy alone has limited effect on peritoneal metastases. The purpose of this work is to fabricate a regional nanomedicine delivery system with injectable hydrogel, to investigate the sustained drug release, biocompatibility, degradation, and the therapeutic efficacy on advanced GC.
The injectable hydrogel gelling at body temperature was synthesized by one-step esterification of albumin and polyethylene glycol. The paclitaxel-loaded nanoparticles (PRNP) were prepared by encapsulating the drug in erythrocytes membrane ghost and embedded into the hydrogel (PRNP-Gel). The physical and chemical performances were characterized by dynamic light scattering, electronic microscope and SDS PAGE. The drug loading content, hemocompatibility, degradation, drug release, drug accumulation at tumor site, and anti tumor efficacy was also investigated.
The PRNP-Gel suspension gelated in 15 min after subcutaneous injection. The diameter of PRNP in hydrogel was 133.1±1.6 nm, drug loading efficacy and content were 85.45±1.32% and 22.10±0.25%, respectively. 37.9% of the loaded paclitaxel was released in 196 h in vitro, demonstrating the sustained release properties of PRNP-Gel. No hemolysis was detected within the concentration up to 10 mg/mL, and the PRNP-Gel degraded completely in 200 days after injection. The IC50 of PRNP against MKN45 gastric cancer cells, determined by MTT, was 15.16 ng/mL. In vivo antitumor evaluation found that, the tumor growth inhibition of MKN45 on tumor bearing mice was 64.5% of PRNP-Gel group, which was higher than the PRNP (40.0%, P
The biocompatible and degradable drug delivery system could release chemotherapeutics in a long-term and sustained manner, exhibited an enhanced drug accumulation at tumor site, resulting in the superior antitumor effect in vitro and in vivo. This work provided a new strategy of therapy for advanced GC.
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National Nature Science Foundation of China
All authors have declared no conflicts of interest.