Use of a Triblock Copolymer Hydrogel for Controlled Release of Cisplatin and BMN-673
Mentor: Robert A Cormack, PhD (Dana Farber Cancer Institute)
This project is working toward the optimization of the treatment of cervical cancer by using the chemotherapy drug, and known radiosensitizer, Cisplatin in conjunction with radiation therapy and PARP inhibitor BMN-673 in a novel manner. Cisplatin is generally administered to patients systemically, resulting in devastating side effects to the patient, including vomiting, hair loss, and nausea. The radiosensitizing effects of Cisplatin are not tissue specific, and as a result, the negative side effects of systemic radiation on healthy tissues can also be devastating for patients. Working in collaboration with Northeastern University, the Dana Farber Cancer Institute, and the Brigham and Women’s Hospital, I will be experimenting with a biologically engineered hydrogel designed to hold a dose of Cisplatin that will be injected into a tumor in the same clinical procedure as brachytherapy so that Cisplatin is delivered to the tumor with minimal harm to healthy tissues in the body. The hydrogel involved in our testing will be a tri-block co-polymer made up of PLGA-PEG-PLGA. The hydrophobic and hydrophilic pocketing of the gel affords us with the opportunity to also experiment with the incorporation of hydrophobic PARP inhibitor BMN-673 as a second drug to be loaded in the gel with hydrophilic Cisplatin. Previous research with this hydrogel as a drug delivering agent has shown that it is non-toxic, biodegradable, capable of gelling at body temperature, and also, capable of drug release over a two week period with optimal release in the first 72 hours. Moving forward with this project I will be working with the hydrogel in vitro and in vivo to characterize and attempt to optimize its effectiveness in Cisplatin uptake and targeted, sustained delivery. Methods for evaluating the hydrogel performance will include evaluating its ability to provide prolonged release of Cisplatin/BMN-673, its capacity to be biodegradable, how thoroughly drugs are released throughout the tumor, and the amount tumor reduction in hydrogel-treated mice as compared to other treatments and a control.
Figure: Schematic of tri-block co-polymer gel (PLGA-PEG-PLGA) loaded with Cisplatin and BMN-673. The hydrophilic Cisplatin (orange circles) is held by the hydrophilic PEG regions (red lines) of the gel while the hydrophobic BMN-673 (blue stars) is held by the hydrophobic PLGA pockets (green lines). The dual nature of the gel allows for the potential to load both a hydrophobic drug and a hydrophilic drug. Source: (Qiao et al. 2005) Source: