Jeannine M Coburn1, Jamie Harris2, Rachel Cunningham3, Jasmine Zeki2, David L Kaplan3, Bill Chiu4. 1. Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA; Department of Biomedical Engineering, Tufts University, Medford, MA, USA. 2. Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA. 3. Department of Biomedical Engineering, Tufts University, Medford, MA, USA. 4. Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: bchiumd@uic.edu.
Abstract
INTRODUCTION: Local drug delivery minimizes systemic toxicity while delivering high-dose chemotherapy for neuroblastoma patients. We hypothesized that varying burst and maintenance dosing of implanted silk platforms would improve survival. METHODS: Platforms were loaded with vincristine 25μg, 50μg, 100μg, and 200μg varying burst (released 1-4days postimplantation) and maintenance (over the next 20days) dosing. Orthotopic tumors were created in mice using human neuroblastoma KELLY cells. Silk platforms were implanted into tumors when volumewas >300mm3. Tumor volume was monitored weekly with ultrasound. Experimental endpoints were tumor volumewas >1000mm3 or weight losswas >25%. RESULTS: Drug release ranged from burst dosing of 18.2 to 80.9μg, maintenance of 5.0 to 111.6μg, and cumulative of 23.3 to 177.4μg. Animals treated with 200μg platform died 9-13days postimplantation, corresponding to 128.1-141.2μg released (toxic dose). Animals received 30.2±3.4μgday-one survived longer than those that received 10.1±1.1μg (p=0.03), suggesting <10.1μgday-one was insufficient. Tumors treated with 100μg or 50μg silk platform took longer to reach 1000 mm3 compared to those treated with control, 44.8±9.5days (p<0.001) and 26.7±6.7days (p<0.05), respectively, versus 7.0±1.7days. Overall survival correlated with higher burst (r=0.446, p=0.004) and maintenance dosing (r=0.353, p=0.02), Animal survival days=30.314+0.626 × (dose on day-one) - 0.020×(tumor volume at day-ten) (p<0.05). CONCLUSION: Platform formulations can be manipulated to vary burst and maintenance dosing, summarized by an equation consisting of these variables.
INTRODUCTION: Local drug delivery minimizes systemic toxicity while delivering high-dose chemotherapy for neuroblastomapatients. We hypothesized that varying burst and maintenance dosing of implanted silk platforms would improve survival. METHODS: Platforms were loaded with vincristine 25μg, 50μg, 100μg, and 200μg varying burst (released 1-4days postimplantation) and maintenance (over the next 20days) dosing. Orthotopic tumors were created in mice using humanneuroblastoma KELLY cells. Silk platforms were implanted into tumors when volumewas >300mm3. Tumor volume was monitored weekly with ultrasound. Experimental endpoints were tumor volumewas >1000mm3 or weight losswas >25%. RESULTS: Drug release ranged from burst dosing of 18.2 to 80.9μg, maintenance of 5.0 to 111.6μg, and cumulative of 23.3 to 177.4μg. Animals treated with 200μg platform died 9-13days postimplantation, corresponding to 128.1-141.2μg released (toxic dose). Animals received 30.2±3.4μgday-one survived longer than those that received 10.1±1.1μg (p=0.03), suggesting <10.1μgday-one was insufficient. Tumors treated with 100μg or 50μg silk platform took longer to reach 1000 mm3 compared to those treated with control, 44.8±9.5days (p<0.001) and 26.7±6.7days (p<0.05), respectively, versus 7.0±1.7days. Overall survival correlated with higher burst (r=0.446, p=0.004) and maintenance dosing (r=0.353, p=0.02), Animal survival days=30.314+0.626 × (dose on day-one) - 0.020×(tumor volume at day-ten) (p<0.05). CONCLUSION: Platform formulations can be manipulated to vary burst and maintenance dosing, summarized by an equation consisting of these variables.
Authors: Jeannine Coburn; Jamie Harris; Alexander D Zakharov; Jennifer Poirier; Naohiko Ikegaki; Andre Kajdacsy-Balla; Monika Pilichowska; Alexander V Lyubimov; Hiroyuki Shimada; David L Kaplan; Bill Chiu Journal: Int J Cancer Date: 2016-11-03 Impact factor: 7.396
Authors: F Philipp Seib; Jeannine Coburn; Ilona Konrad; Nikolai Klebanov; Gregory T Jones; Brian Blackwood; Alain Charest; David L Kaplan; Bill Chiu Journal: Acta Biomater Date: 2015-04-08 Impact factor: 8.947
Authors: Jasmine Zeki; Jordan S Taylor; Burcin Yavuz; Jeannine Coburn; Naohiko Ikegaki; David L Kaplan; Bill Chiu Journal: Surgery Date: 2018-07-27 Impact factor: 3.982
Authors: Jordan S Taylor; Burcin Yavuz; Jasmine Zeki; Lauren Wood; Naohiko Ikegaki; Jeannine Coburn; Kristin Harrington; Hiroyuki Shimada; David L Kaplan; Bill Chiu Journal: Surgery Date: 2020-02-28 Impact factor: 3.982
Authors: Kimberly J Ornell; Jordan S Taylor; Jasmine Zeki; Naohiko Ikegaki; Hiroyuki Shimada; Jeannine M Coburn; Bill Chiu Journal: Cancer Med Date: 2020-02-24 Impact factor: 4.452