Encapsulation of a Small Hydrophilic Drug in Injectable PLGA Microparticles for Treatment of Pancreatic Cancer

Abstract

Pancreatic cancer is the fourth largest cause of cancer-related deaths in Canada, and has the highest mortality rate of all major cancers. The typical methods of treatment: chemotherapy and radiation have significant side effects, as they do not target the tumour specifically. Targeted therapies are being developed that would specifically affect the pancreatic tumour, leaving healthy cells undamaged. A small, hydrophilic drug has been shown to inhibit the activity of Neu1 sialidase, an enzyme involved in the activation of the growth process, which is upregulated in tumour cells. Previous research has shown that encapsulation of the drug in a surgically implanted PLGA capsule allows for drug release over a period of several weeks, inhibiting tumour growth. A microparticle form is desired, to decrease the invasiveness of the treatment. Encapsulation of the drug was performed using an aqueous double-emulsion method, resulting in a drug encapsulation efficiency of 37%. A mean particle size of 125 was obtained, within the range acceptable for injectable particles. Further experiments will be performed to compare the encapsulation efficiency with microparticles prepared using an organic single-emulsion method. The release kinetics of the drug will be characterized in vitro using HPLC analysis, and its effectiveness in inhibiting tumour growth will be assessed using tumour cell cultures and animal models. Should this dosage form prove effective at inhibiting tumour growth, it may lead to the formulation of an injectable dosage form capable of sustained release.