Disseminated injection of vincristine-loaded silk gel improves the suppression of neuroblastoma tumor growth

Background: Advanced-stage neuroblastoma patients require multiagent chemotherapy. Intratumoral implantation of vincristine-loaded silk gel uses local diffusion to decrease orthotopic neuroblastoma tumor growth in mice. We hypothesize that injecting vincristine-loaded silk gel into 8 locations within the tumor, instead of only centrally, decreases the diffusion distance and improves tumor growth suppression. Methods: Human neuroblastoma cells, KELLY, were injected into mouse adrenal glands to create orthotopic tumors. After the tumors reached 100 mm3by ultrasound, silk gels loaded with 50 µg vincristine were injected centrally or in 8 areas throughout the tumor. Drug-release profile was measured in vitro. Endpoints were tumor size >1,000 mm3and histologic examination. Results: Vincristine-loaded silk gels suppressed tumor growth up to an inflection point (458.7 ± 234.4 mm3for central, 514.3 ± 165.8 mm3for 8-point injection) before tumor growth accelerated >200 mm3over 3 days. The time to inflection point was 6.6 days for central, 13.3 days for 8-point injection (P <.05). Using the sphere volume equation to approximate tumor volume, splitting the volume into 1/8 decreased the diffusion radius by 1/2. Histologic examination confirmed tumor necrosis adjacent to vincristine-loaded silk gel. Conclusion: Injecting vincristine-loaded sustained release silk gel at 8 separate locations halved the diffusion distance and doubled the time for the tumor to reach the growth inflexion point.