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In vitro and in vivo evaluation of etoposide - silk wafers for neuroblastoma treatment
- Source :
- Journal of Controlled Release. 285:162-171
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- High-risk neuroblastoma requires surgical resection and multi-drug chemotherapy. This study aimed to develop an extended release, implantable and degradable delivery system for etoposide, commonly used for neuroblastoma treatment. Different concentrations of silk, a biodegradable, non-toxic, non-immunogenic material were employed to prepare etoposide-loaded wafer formulations. Secondary structure of silk in the formulations was characterized using Fourier Transform Infrared (FTIR) spectroscopy and optimized based on the crystalline structure. Accelerated in vitro degradation studies under different conditions such as acidic, alkaline, oxidizing mediums and high temperature, were performed. The integrity of the silk wafer structure was maintained unless exposed to 0.1 N NaOH for 24 h. In vitro release of etoposide was performed in PBS (phosphate buffered saline) at 37 °C. Silk coated 6% wafers released the drug up to 45 days, while uncoated wafers released the drug for 30 days. Cytotoxicity study was performed on KELLY cells to evaluate the etoposide cytotoxicity (LC50) and the long-term efficacy of the etoposide wafer formulations. The results showed that etoposide killed 50% of the cells at 1 μg/mL concentration and the wafer formulations demonstrated significant cytotoxicity up to 22 days when compared to untreated cells. Using an orthotopic neuroblastoma mouse model, intra-tumoral implantation of the coated 6%, uncoated 6%, or uncoated 3% silk wafers were all effective at decreasing tumor growth. Histological examination revealed tumor cell necrosis adjacent to the drug-loaded silk wafer.
- Subjects :
- Silk
Mice, Nude
Pharmaceutical Science
02 engineering and technology
Article
Neuroblastoma
03 medical and health sciences
Drug Delivery Systems
0302 clinical medicine
In vivo
Cell Line, Tumor
medicine
Animals
Humans
Wafer
Cytotoxicity
Etoposide
Drug Implants
Chemistry
Bombyx
021001 nanoscience & nanotechnology
medicine.disease
Antineoplastic Agents, Phytogenic
In vitro
SILK
Delayed-Action Preparations
030220 oncology & carcinogenesis
Drug delivery
Female
0210 nano-technology
medicine.drug
Nuclear chemistry
Subjects
Details
- ISSN :
- 01683659
- Volume :
- 285
- Database :
- OpenAIRE
- Journal :
- Journal of Controlled Release
- Accession number :
- edsair.doi.dedup.....973e2d0148ff962b453540d9676207bc
- Full Text :
- https://doi.org/10.1016/j.jconrel.2018.07.002