Assessment of Lipid Nanocapsules and Liposomes as Nanocarriers for C6 Ceramide Delivery to Breast Cancer Cells

Sekaringtyas, Fransiska Christydira (2024). Assessment of Lipid Nanocapsules and Liposomes as Nanocarriers for C6 Ceramide Delivery to Breast Cancer Cells. University of Birmingham. M.Sc.

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Abstract

Ceramides, a class of bioactive sphingolipids, have been shown to contribute to various cellular and signalling events. C6, as a short-chain ceramide, is considered the most potent ceramide which can inhibit proliferation and induce pro-apoptotic effects in specific cancer cells, including triple-negative breast cancer (TNBC). However, the therapeutic application of ceramides is limited due to their poor water-solubility and susceptibility to enzymatic degradation. Therefore, encapsulating ceramides into nanoparticles may be required to increase intracellular levels and generally enhance ceramide efficacy. This study investigates the use of lipid nanocapsules (LNCs) as a suitable alternative to liposome for ceramide delivery. The presence of C6 ceramide had no major impact on the physico-chemical properties of LNCs, but did affected liposome properties. LNCs formulations had greater stability under storage (at 4℃) and cell culture conditions than liposomes. Also, liposomes were more likely to aggregate at high salt concentrations. C6 ceramide-loaded nanoparticles (LNCs-C6 and liposome-C6) were more cytotoxic than equivalent ghost nanoparticles (LNCs-ghost and liposome-ghost) towards MDA-MB-231 breast cancer cells. C6 ceramide was confirmed to induce cancer cell death through apoptosis and caspase-3/7 activation. Encapsulating ceramide did not limit its pharmacology activity on TNBC cells, and in some cases mildly enhanced its efficacy with LNCs-C6 seen to be slightly more effective than liposome-C6. These results provide further insight into the application of LNCs as a compatible nanocarrier for ceramide delivery and offer a viable platform for future development of anticancer drug-loaded ceramide LNCs for combination therapy in cancer treatment.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):