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The Ohio State University

1. Cosby, Lauren E. Preclinical Delivery of Fractionated Black Raspberry Phytochemicals to Oral Epithelial Cells Using Lipid and Polymer Nanoparticles.

Degree: PhD, Biomedical Engineering, 2019, The Ohio State University

Oral cancer is the sixth most prevalent cancer worldwide with an estimated 643,000 new cases occurring annually. Through in vitro, in vivo and human clinical trial studies, black raspberries (BRBs) and their bioactive components have exhibited significant anticancer activities in oral cancer tissues. These properties, including growth inhibition and anti-inflammatory effects, are attributed to the complex mixture of phytochemicals present in ripe BRBs and their combinatorial interactions. These studies aim to engineer and characterize delivery vehicles for lutein and evaluate lutein biological activity, a phytochemical identified in the lipophilic BRB fraction. We hypothesize that lutein encapsulation employing lipid and polymer nanoparticles will improve in vitro bioavailability, facilitate growth inhibition, modulate release kinetics, and regulate gene expression signatures in premalignant cells that support oral cancer chemopreventive activities. The effect of whole, ripe, freeze-dried BRBs on aerodigestive carcinogenesis continues to be an active topic for cancer prevention research. Additionally, the roles for anthocyanin-rich hydrophilic compounds are often emphasized due to their inherent bioavailability. However, recently our research focus includes the poorly bioavailable carotenoid-rich lipophilic phytochemicals. In order for these lipophilic compounds to be accurately evaluated for anticancer efficacy, it is necessary to increase their bioavailability by facilitating their delivery to target tissues. Nanoparticle (NP) formulations were designed and evaluated for their capacity to efficiently encapsulate lutein. NPs were made by sonication and electrohydrodynamic mediated mixing nanoprecipitation (EM-NP) methods using PHOSPHOLIPON 90G® (P90G, Lipoid GmbH), polystyrene-polyethylene oxide (PS-PEO) or polycaprylactone-polyethylene glycol (PCL-PEG) co-block polymers. NP characterization included encapsulation efficiency (EE), size distribution and cellular uptake. All biological activities were conducted in normal (TE1177) and premalignant (SCC83) oral cells and assessed growth, cytotoxicity, viability, cell cycle phase and gene expression effect. Data demonstrated NP production via EM-NP produced higher EE than sonication and P90G had the greatest EE and elicited faster cellular uptake of lutein compared to the other delivery systems. Lutein PCL-PEG micelles (LNPs) exhibited 44% growth inhibition in SCC83 cells and did not elicit a substantial toxic effect or impact cell viability. LNPs caused an increase in DNA accumulation in the G1 phase for TE1177 cells but did not affect SCC83 cell cycle. LNPs did not affect gene expression in normal cells but upregulated apoptosis and autophagy activity and downregulated growth and angiogenesis biomarkers in SCC83 cells. These data support the need for drug delivery vehicles in enhancing bioavailability of lutein and suggest lutein promotes anticancer activity in premalignant oral epithelial cells. Advisors/Committee Members: Winter, Jessica (Advisor), Weghorst, Christopher (Committee Co-Chair).

Subjects/Keywords: Biomedical Engineering; Public Health; lutein; EMNP; oral cancer; drug delivery; polymer micelles; lipid micelles

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APA (6th Edition):

Cosby, L. E. (2019). Preclinical Delivery of Fractionated Black Raspberry Phytochemicals to Oral Epithelial Cells Using Lipid and Polymer Nanoparticles. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1555521088604392

Chicago Manual of Style (16th Edition):

Cosby, Lauren E. “Preclinical Delivery of Fractionated Black Raspberry Phytochemicals to Oral Epithelial Cells Using Lipid and Polymer Nanoparticles.” 2019. Doctoral Dissertation, The Ohio State University. Accessed September 19, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555521088604392.

MLA Handbook (7th Edition):

Cosby, Lauren E. “Preclinical Delivery of Fractionated Black Raspberry Phytochemicals to Oral Epithelial Cells Using Lipid and Polymer Nanoparticles.” 2019. Web. 19 Sep 2019.

Vancouver:

Cosby LE. Preclinical Delivery of Fractionated Black Raspberry Phytochemicals to Oral Epithelial Cells Using Lipid and Polymer Nanoparticles. [Internet] [Doctoral dissertation]. The Ohio State University; 2019. [cited 2019 Sep 19]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1555521088604392.

Council of Science Editors:

Cosby LE. Preclinical Delivery of Fractionated Black Raspberry Phytochemicals to Oral Epithelial Cells Using Lipid and Polymer Nanoparticles. [Doctoral Dissertation]. The Ohio State University; 2019. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1555521088604392

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