Alexis Robinson with Dr. Sri Sridhar (NU)
Talazoparib (TLZ), a potent PARP inhibitor, has shown clinical and pre-clinical activityby inducing synthetic lethality in cancers with germline Brac 1 or 2 mutations. However, the hydrophobic nature of TLZ along with its oral delivery route limits its bioavailability;necessitating high doses leading to off-site toxicity. Advances in drug delivery systems have progressed through the usage of biodegradable polymers, specifically Poly (lactic – co – glycolic)acid (PLGA). The tunable mechanical and degradation properties of PLGA add to its appeal as a vehicle for improving the bioavailability of chemotherapy reagents at the tumor site and minimizing any leaking from the tumor to decrease the potential off-target toxicity.The use of biodegradable PLGA implants in the use of cancer treatment prolongs drug delivery with minimal systemic side effects. The in vivo therapeutic efficacy of Talazoparib implants is to be assessed following intraperitoneal injection in immunodeficient nude mice compared to drug – free implants. In vitro studies with murine fallopian tube (mFT) cell lines will be conducted as well. Localized and sustained delivery of Talazoparib via implants have the potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity to patients.