(525h) Design of Dual Encapsulated Biodegradable Nanoparticles for Cancer Treatment

One drawback to chemotherapy is that drugs currently approved by the United States Food & Drug Administration (FDA) for therapeutic treatment of cancer, such as paclitaxel, typically have poor aqueous solubility and require toxic solvents such as polyethoxylated castor oil (trademark Kolliphor® EL) [1]. This leads to adverse side effects such as fatigue, hair loss, easy bruising and bleeding, infection, anemia, nausea and vomiting, and appetite changes. Second, in order to overcome enzymatic degradation of the drug and reach therapeutic efficacy at the disease site, patients must receive large doses, usually a “cocktail” of steroids and several anticancer drugs, adding to the severity of side effects. Third, clinical practice dictates that a trained professional at a clinic or hospital gives these drugs intravenously as a bolus dose over a series of weeks. Patients and their caregivers must then take time off of work and even travel long distances for proper medical care, increasing the magnitude of medical expenses. Given these disadvantages with the standard treatment of cancer, a nanoparticle formula, which combines two or more anticancer agents, could be beneficial.

Nanoparticle drug delivery shows much promise in vitro and in vivo as it provides a foundation that can be easily tailored depending on the characteristics of the disease. Modifications such as size, shape, material composition, drug payload, and targeting moieties affect the cellular internalization and drug release kinetics as well as the therapeutic efficacy. As such, this research aims to show and optimize the factors that most affect particle size, polydispersity, drug encapsulation efficiency, and drug release profile. These factors include solvent/polymer interactions, synthesis method, polymer chemistry, and polymer molecular weight. To study processing parameters, nanoparticles are produced with flash precipitation method using polystyrene as the model polymer and several agents with varying degrees of hydrophobicity (i.e. FITC, Rhodamine B, DiD’ oil) as the model drug. Response measurements include dynamic light scattering (DLS) and scanning electron microscopy (SEM) for nanoparticle characterization. Previously the authors used a Box-Behnken experimental design to study the effect of injection flow rate, solvent to anti-solvent ratio, and stir rate on nanoparticle size by controlled precipitation of polystyrene. This allowed the development of a predictive equation. Using this model equation, both 200 and 300 nm particles were synthesized with low batch-to-batch variability in particle size and consistent distribution of particles.

The knowledge gained from these experiments will be utilized for the formulation of biodegradable nanoparticles with dual encapsulation of chemotherapeutic (paclitaxel) and antiangiogenesis agent (fumagillin) [2]. Future work will include evaluating the efficacy of these formulations in cancer treatment.

1. Gelderblom, H., et al., Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer, 2001. 37(13): p. 1590-8.
2. Kornienko, A., et al., Toward a Cancer Drug of Fungal Origin. Med Res Rev, 2015. 35(5): p. 937-67.