2022 Annual Meeting
Mesoporous Organosilica Nanoparticles As a Promising Carrier to Enhance Efficacy/Safety Ratio for Advanced Ovarian Cancer
According to the American Cancer Society many anti-cancer drugs including chemotherapeutics (such as paclitaxel, irinotecan, and thioguanine) and targeted therapeutics (Afatinib and Olaparib) used in clinics are hydrophobic and suffer from low bioavailability so higher repetitive doses are needed. For these reasons, biocompatible carriers are needed to protect the drug and increase its bioavailability. Advanced stage ovarian cancer in women involves intraperitoneal injection (IP) of high doses of chemotherapeutic drugs which generally results in severe side effects. Therefore, new drug combination that lessen the chemotherapy dose but maintain same efficacy are attractive. Afatinib, a tyrosine kinase inhibitor is currently used as a first line treatment for non-small cell lung cancer (NSCLC) and being investigated for Her2 positive breast cancer. Serous epithelial ovarian cancer express Her2/neu mutations [1], indicating that Afatinib can be a promising therapy. We have developed lipid-coated organosilica nanoparticles that efficiently load the hydrophobic drugs and screened the efficacy to BR5 mice ovarian cancer cells of various drug combination in presence of Afatinib. We have used transmission electron microscopy and ZetaSizer to assess the shape and colloidal stability of the nanoparticles, cell titer glo assay for in vitro efficacy of the drug combination, plate reader and nanodrop of drug loading, IVIS for in vivo studies where preliminary data has shown promising results in Afatinib and paclitaxel combination loaded in nanoparticles on IP injected mice.
[1] Alvarez et al Gynecol Oncol Rep. 2019 Aug; 29: 70â72