Author

Emily Martin

Date on Master's Thesis/Doctoral Dissertation

7-2016

Document Type

Master's Thesis

Degree Name

M. Eng.

Department

Bioengineering

Committee Chair

Soucy, Patricia

Committee Co-Chair (if applicable)

Ehringer, William

Committee Member

Ehringer, William

Committee Member

Gerber, Erin

Abstract

Excess production of Reactive Oxygen Species (ROS), which can be caused by radiation, cigarette smoke, and pollutants, can cause many damaging cellular effects, such as DNA damage and unregulated cell apoptosis. If left unmitigated, chronic overproduction of ROS has been linked to the formation of cancer, diabetes, atherosclerosis, rheumatoid arthritis, chronic inflammation, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and amyotrophic lateral sclerosis. ROS is typically eliminated with antioxidants, which scavenge and inhibit the formation of ROS by becoming oxidized by the ROS and by binding to its precursors.

Curcumin is an effective lipid-soluble antioxidant agent. However, its poor bioavailability, rapid metabolism by the liver and intestinal tract, and short biological half-life greatly hinders its therapeutic abilities. The water soluble antioxidant, n-2-mercaptoproprionyl glycine (N-MPG), also has been found to scavenge ROS and decrease lipid peroxidation. Like curcumin, its therapeutic efficacy is limited due to its poor half-life. In order to improve bioavailability and stability of these two antioxidants, lipid vesicle formulations have been designed and characterized for transdermal delivery of the antioxidants. Transdermal delivery is a pain-free method of drug delivery that allows the antioxidants to permeate through the skin layers for systemic delivery.

Three lipid vesicle formulations, traditional liposomes, ultradeformable liposomes, and ethosomes, have been fabricated and characterized in order to determine which vesicle type has the highest skin permeation through the stratum corneum. Each of the three lipid vesicle formulations were composed of 10 mg/ml Soy-PC, 0.48 mg/ml vii

curcumin, and 1 mg/ml N-MPG. The ultradeformable vesicles incorporate an edge activator, 1.5 mg/ml cholic acid, into its structure to increase deformability of the vesicles. The ethosomes are vesicles composed in a 40% ethanol solution to increase the fluidity of the vesicles and skin membrane. The vesicles were characterized for size, stability, morphology, and entrapment efficiency. A modified Franz-Diffusion Chamber was used to test the skin permeability of each vesicle type.

Each particle type was fabricated to have a diameter less than 200 nm. The unloaded particle types were tested for stability using a PeroxiDetect Assay, which detected amount of lipid hydroperoxides. The ethosomes had the least amount while the ultradeformable liposomes had the most. However, when analyzing size of the vesicles over various time points, the ultradeformable liposomes were the most stable. Every vesicle type had a semi-spherical morphology, with the ultradeformable liposomes having the smoothest morphology. The ethosomes had the highest entrapment efficiency of curcumin (statistically similar to the traditional liposomes) and N-MPG.

The modified Franz-Diffusion chamber was used to characterize skin deposition of the vesicles. At hour 2, the ethosomes had the highest fluorescence and consequently, skin deposition. At hour 24, the traditional liposomes, which were statistically similar to the ultradeformable liposomes, had the highest skin deposition. In the image analysis, the ethosomes had the highest sum intensity in the stratum corneum. In the epidermis, the traditional liposomes, which were statistically similar to the ethosomes, had the highest sum intensity. The traditional liposomes had the highest sum intensity in the dermis layer. Subsequently, the ethosomes are recommended for short-term applications of curcumin and N-MPG while the traditional liposomes are recommended for long-term applications.

Available for download on Monday, July 31, 2017

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