Date on Master's Thesis/Doctoral Dissertation

5-2014

Document Type

Master's Thesis

Degree Name

M. Eng.

Department

Bioengineering

Committee Chair

Soucy, Patricia Sara Arauz

Author's Keywords

Curcumin; Albumin; Spray drying; Crosslinking

Subject

Albumins; Drug delivery systems

Abstract

In space, astronauts are exposed to a large doses of ionizing radiation which can cause various health problems. The drug delivery of antioxidants and anti-inflammatory substances is a promising countermeasure for the harmful cellular effects of radiation exposure. Curcumin is a polyphenol derived from the rhizome of the turmeric plant that has strong antioxidant capabilities. The therapeutic potential of this radical scavenging drug is limited by poor uptake in the body due to its insolubility in water, rapid metabolism by the intestinal mucosa and liver, and quick excretion. Drug delivery vehicles can be used to enhance the bioavailability of curcumin. Albumin, a biodegradable and non-immunogenic plasma protein, can be utilized as a drug delivery vehicle. Curcumin binds to albumin’s hydrophobic pockets, which increases its solubility and decreases its rate of degradation in physiological conditions. Curcumin was solubilized with 0.5% (w/v) fatty acid free human serum albumin (FAF HSA) and spray dried to form a dry powder of particles. To produce particles with a smooth and spherical morphology, 0.05% (v/v) Tween® 20 was included in the solution. Curcumin release from these particles followed a first-order release profile (Ct/Cinf = 1 - ekt, t = time in min) with k = 0.065 ± 0.003. To alter the release of curcumin from the spray dried particles, 0.5% FAF HSA was crosslinked using 0.01M 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and 5 mM Nhydroxysulfosuccinimide. This crosslinking method was confirmed by native polyacrylamide gel electrophoresis (PAGE) and differential scanning calorimetry (DSC). For the native PAGE results, multiple protein bands at high molecular weights were observed for the crosslinked FAF HSA and a single protein band for the uncrosslinked FAF HSA. This suggested that multiple FAF HSA molecules had been crosslinked to each other. DSC results reported a significant increase in melting point from 53.60 ± 1.35 °C to 63.82 ± 2.34 °C of spray dried FAF HSA particles, further confirming the crosslinking method. Curcumin was bound to the crosslinked FAF HSA in the presence of 0.05% Tween® 20 and spray dried. The resulting particles showed a less uniform morphology and curcumin release followed a first-order profile with a significantly lower k = 0.049 ± 0.004. Future work to improve the morphology of the crosslinked FAF HSA particles and increase the level of crosslinking to further slow curcumin release will enhance the applicability of these particles in mitigating radiation-induced cell damage.

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