Developing an Injectable Glycosaminoglycan-Based Drug Delivery System for Neuroblastoma

Chilamkurthi, Akhil; Carleton, Emelia; Avakian, Christina; Voronin, Andrew

Student Work

Developing an Injectable Glycosaminoglycan-Based Drug Delivery System for Neuroblastoma

Public Deposited

Neuroblastoma is an embryonic cancer derived from the sympathetic nervous system that typically targets children under the age of 5, it is the most common and deadly solid tumor in children. High dose chemotherapy is the primary treatment for neuroblastoma patients; however, it is administered systemically and kills off-target cells, leading to a multitude of undesirable effects. In comparison to chemotherapy, intra-tumoral drug administration is a more suitable option to deliver therapeutics since it can be administered at high concentrations locally, while limiting off-target cytotoxicity. Hydrogel-based drug delivery systems are expected to be an efficient model to produce a locally administered controlled drug release system with a sustained release. The goal of this project is to identify, design, fabricate, and validate a chondroitin sulfate-based hydrogel drug delivery system with an acceptable injection force and drug release profile for localized intra-tumoral delivery of chemotherapeutic agents. Three design approaches were taken into consideration before the final hydrogel formulation was chosen based on the various design constraints determined during the initial stages of this project. Efficacy of the final hydrogel formulation was then evaluated via swelling, degradation, drug loading, drug release, injection force, and dimethyl-methylene blue assays. It was concluded that CS – Linear PEG-MI and CS – Tetra PEG-MI hydrogels were able to produce a hydrogel drug delivery system that not only showed compatibility with daunorubicin loading but also maintained a low injection force and insolubility throughout. In addition, both CS – Linear PEG-MI and CS – Tetra PEG-MI hydrogels showed reproducible drug loading and drug release profiles over a 28-day timeline, respectively. Injection force testing using a 2 kN Instron showed that CS – Linear PEG-MI produced softer gels with an injection force of 7.95 ± 1.67N, in comparison to the CS – Tetra PEG-MI hydrogels which were more rigid and produced an injection force of 18.63 ± 3.88 N. Upon further testing, it was determined that loading the hydrogels with daunorubicin, CS – Tetra PEG-MI experienced greater loading, on average, compared to CS – Linear PEG-MI. Variability in drug release readings for both samples created a challenge when comparing the drug release profiles, although further analysis is needed, CS – Linear PEG-MI hydrogels produced a quicker rate of release during the early timepoints. Despite meeting objectives, further conclusions and recommendations were made to help establish what can be done to improve and optimize the drug delivery system design.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

Creator

Publisher