FORMULATION AND CHARACTERIZATION OF TOLFENAMIC ACID ENCAPSULATED PLGA NANOPARTICLES FOR CANCER THERAPY

Purpose: Tolfenamic acid, an NSAID, is derived from the willow tree. It is water insoluble and has low bioavailability in humans. Nanotechnology can help increase the bioavailability of water insoluble compounds. This research project will demonstrate the cellular uptake and bioavailability of poly(lactic-co-glycolic acid) nanoparticles with tolfenamic acid. In the future, results from this study can be applied to other water insoluble, plant derived compounds for cancer therapy. Hypotheses: 1) Tolfenamic (TFA) PLGA nanoparticles (np) will have a higher bioavailability than free tolfenamic acid and be more efficacious for cancer therapy. 2) TFA-PLGA np formulated with binary solvent will have a higher encapsulation efficiency than pure organic solvent. Methods: Methods included particle size analysis, calculating encapsulation efficiency and drug loading, cellular uptake of TFA-PLGA np, effect of TFA-PLGA np on cell lines (Panc-1, MiaPaCa, and BxPC3), and effect of TFA-PLGA np on cell migration. Results: Results: The encapsulation efficiency was found to be 65-75% with ethyl acetate. With the binary solvent formulation, encapsulation efficiency increased to 94%.Robust intracellular uptake was seen in three different pancreatic cell lines. MTT assay revealed that IC50 values for TFA-PLGA np was 120 µM as compared to 372 µM for free TFA. Scratch assay revealed that TFA-PLGA np had inhibitory effect on migration of pancreatic cancer cells. Conclusions: Conclusions: TFA PLGA np had a higher bioavailability and will be more efficacious for cancer therapy than free TFA. The migration assay also indicated that the TFA np had reduced invasive potential.