Author

Brian Gettler

Date on Master's Thesis/Doctoral Dissertation

12-2014

Document Type

Master's Thesis

Degree Name

M. Eng.

Department

Bioengineering

Committee Chair

Soucy, Patricia

Committee Member

Ehringer, William

Committee Member

O'Toole, Martin

Committee Member

Quesada, Peter

Abstract

Radiation exposure is both a major obstacle in space exploration and an occupational hazard for various careers causing DNA damage and ROS. In order to reduce the effects of radiation, the primary and most explored approach has been focused around mitigation in terms of exposure duration, exposure intensity, and shielding usage. In some situations none of these reduction strategies were viable and so the use of antioxidants is being explored as an alternate strategy for therapeutic purposes. One such antioxidant is curcumin, otherwise known as diferuloylmethane, is a component of turmeric with both antioxidant properties and anti-inflammatory properties. Another antioxidant that could be used to scavenge free radicals, n-Acetylcysteine (NAC), is both a pharmaceutical drug and a dietary supplement. Finally n-2-mercaptopropionyl glycine (N-MPG) is an antioxidant used in the treatment of kidney stones. These radioprotectants are used primarily to mitigate ROS induced by radiation but have short half-lives in physiological conditions and poor bioavailability. Liposomes can be used to entrap materials such as NAC, N-MPG, and curcumin. Liposomes can entrap hydrophobic molecules such as curcumin within the bilayer itself or hydrophilic materials such as NAC and N-MPG within the aqueous interior of the liposome. Liposomes can be used to deliver their contents to cells via membrane fusion. Small unilamellar vesicles (SUVs) were fabricated by sonication for this purpose and SUVs were evaluated according to size, toxicity, and antioxidant capacity. Dynamic Light Scattering (DLS) measurements showed that the limiting hydrodynamic radius of the SUVs had been reached for all conditions. Limiting hydrodynamic radius was approximately 130nm for Soy-PC/DOTAP loading conditions and approximately 140nm for DOPC/POPA loading conditions. SEM imaging confirmed both spherical and unilamellar morphology of SUVs. Theoretical encapsulation efficiency (EE) was near 100% for curcumin loading conditions. For both NAC and NMPG, EEs were calculated to be 0.88% and 0.90% for Soy-PC/DOTAP and DOPC/POPA loading conditions respectively. MTT assays showed no significant cytotoxicity at the concentrations of both antioxidant and lipid that were used for future evaluations. Amplex Red assay results showed that the fabrication process did not significantly reduce the antioxidant capacity of Soy-PC/DOTAP loaded with NAC or curcumin. Based on these results, it was recommended that Soy-PC/DOTAP loaded with curcumin be investigate for further use.

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