(571w) Semi-Degradable Nanofiber Composites for Delivery of Paclitaxel

Chemotherapeutic engineering is a term used to describe the application of chemical engineering principles such as process and system design to enhance efficacy of chemotherapy treatment for cancer and other diseases. Significant research is being done to develop new treatments such as targeted chemotherapy using cellular markers and circulating nanoparticles. Another important aspect of chemotherapeutic engineering is improving delivery methods for currently available treatments.

Paclitaxel is often referred to as one of the most important advances in chemotherapy in years. The extremely hydrophobic nature of paclitaxel however poses significant problems to traditional delivery methods. The only currently available dosage form utilizes the adjuvant Cremophor EL (a polyoxyethylated castor oil and dehydrated alcohol blend) which itself has been shown itself to be detrimental, with side effects including but not limited to neurotoxicity, nephrotoxicity, cardiotoxicity, and hypersensitivity. Cremophor EL has even been shown to inhibit the action of paclitaxel at certain concentrations.

To achieve controlled local delivery of paclitaxel a semi-degradable composite utilizing degradable electrospun nanofibers and microspheres of poly(lactic-co-glycolic acid) embedded within a macroporous poly(vinyl alcohol) hydrogel has been proposed. Through a combination of degradation and diffusion local paclitaxel delivery can be achieved over the course of 36 days.

A family of paclitaxel loaded PLGA fibers and microspheres were created utilizing traditional electrospraying methods. By varying polymer and concentrations, fibers and particles of varying diameters were achieved. These fibers were analyzed for loading and release kinetics using high performance liquid chromatography, HPLC. Fibers were then loaded into PVA hydrogels using suspension and freeze/thaw cycles to induce physical cross-linking. These composite systems were evaluated for mechanical properties and surface characteristics to determine distance between cross-links and porosity. The systems were then incubated in PBS maintained at 37C for various time points from 1 day to 6 weeks. The release media was sampled and analyzed using HPLC for release kinetics. The entire release media was then incubated with A549 (human lung carcinoma) and MCF-7 (human breast carcinoma) cell cultures. Following two days incubation cells were analyzed for apoptosis using acridine orange/ethidium bromide double staining.