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• W2000299181 abstract "Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAThe role of fish oil (FO) rich in omega-3 fatty acids (n-3 FA) in breast cancer prevention remains controversial. Our data showing that higher ratios of n-3 FA:n-6 FA (in excess of 10:1) are necessary to inhibit rat mammary carcinogenesis suggest that a component of FO may be responsible for its tumor protective effect. DHA may be the critical n-3 FA present in FO since it has been shown to be superior to EPA in inhibiting mammary carcinogenesis. However, the typical Western Diet with a ratio of 1:15 n-3 FA:n-6 FA is not sufficient in providing the amount of DHA required for cancer prevention. In addition, mammals can't synthesize this fatty acid; thus further emphasizing the need for developing a translationally relevant formulation of DHA which can be used for breast cancer prevention in humans. A liposomal formulation for DHA for intravenous administration has been developed, but this route of administration is not appropriate for clinical application as a chemopreventive agent. We hypothesize that the oral liposomal formulation of DHA which is resistant to oxidation and low gastric pH would be ideal since it will enhance its bioavailability in the circulation and at the breast tissue, and thus enhance the chemopreventive efficacy. As an initial approach to test our hypothesis, we developed a liposome that contains lipids similar in structure to lipids found in Archaea, which is known to endure high acidity and temperature. Thus, ether lipids 1,2-di-O-hexadecyl-sn-glycero-3-phosphocholine and 1,2-di-O-phytanyl-sn-glycero-3-phosphoenatholamine were utilized to develop our liposomal formulation via the extrusion method. Our results revealed that the average size of the DHA ether liposome, determined by Dynamic Light Scattering, is approximately 135nm, while that of the ghost formulation is approximately 150nm. This size is ideal for oral administration and can cross the enterocytes of the intestine. The encapsulation efficiency of the liposomes as determined by HPLC-MS/MS is approximately 80%. We showed for the first time that our formulation is resistant to oxidation and stable at various pH (1.0-7.4) at room temperature and at 37°C for a duration of more than two hours. Next, we tested the antitumor action of the liposomal DHA and compared it to that of DHA in the triple negative MDA-MB-231 breast cancer cell line. We observed that liposomal DHA was ten times more potent at inhibiting cell proliferation in culture than non-liposomal DHA. In summary, we report for the first time a liposomal formulation of DHA that can withstand a low pH, thus making its oral delivery feasible. Furthermore, its remarkable growth inhibitory activity at a much lower dose than non-liposomal DHA suggests that our nanotechnology-based approach is a promising strategy to be tested for breast cancer prevention. (Support: Susan G. Komen For the Cure, KG081632 )Citation Format: Christine Gail Skibinski, Arunangshu Das, Mark Kester, Kun-Min Chen, Andrea Manni, Karam El-Bayoumy. A novel biologically active acid stable liposomal formulation of docosahexaenoic acid (DHA) for breast cancer prevention. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5421. doi:10.1158/1538-7445.AM2014-5421" @default.
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• W2000299181 date "2014-09-30" @default.
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• W2000299181 title "Abstract 5421: A novel biologically active acid stable liposomal formulation of docosahexaenoic acid (DHA) for breast cancer prevention" @default.
• W2000299181 doi "https://doi.org/10.1158/1538-7445.am2014-5421" @default.
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