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008200131s2019 ||||||||||||||||| ||eng d
020 ▼a 9781687972248
035 ▼a (MiAaPQ)AAI27602810
035 ▼a (MiAaPQ)OhioLINKosu1555521088604392
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 620.5
1001 ▼a Cosby, Lauren Elizabeth.
24510 ▼a Preclinical Delivery of Fractionated Black Raspberry Phytochemicals to Oral Epithelial Cells Using Lipid and Polymer Nanoparticles.
260 ▼a [S.l.]: ▼b The Ohio State University., ▼c 2019.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2019.
300 ▼a 167 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
500 ▼a Advisor: Winter, Jessica.
5021 ▼a Thesis (Ph.D.)--The Ohio State University, 2019.
506 ▼a This item must not be sold to any third party vendors.
520 ▼a 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 90G짰 (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.
590 ▼a School code: 0168.
650 4 ▼a Public health.
650 4 ▼a Biomedical engineering.
650 4 ▼a Physiology.
650 4 ▼a Medicine.
650 4 ▼a Epidemiology.
650 4 ▼a Oncology.
650 4 ▼a Health sciences.
650 4 ▼a Nanotechnology.
690 ▼a 0541
690 ▼a 0573
690 ▼a 0566
690 ▼a 0992
690 ▼a 0652
690 ▼a 0564
690 ▼a 0766
690 ▼a 0719
71020 ▼a The Ohio State University. ▼b Biomedical Engineering.
7730 ▼t Dissertations Abstracts International ▼g 81-06B.
773 ▼t Dissertation Abstract International
790 ▼a 0168
791 ▼a Ph.D.
792 ▼a 2019
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15494549 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1008102
991 ▼a E-BOOK