Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/21061
Title: Liposomal co-encapsulation of quercetin with synergistic chemotherapeutic drugs for breast cancer treatment
Authors: WONG MAN YI
Keywords: lliposomes, synergism ,cancer
Issue Date: 5-Aug-2010
Source: WONG MAN YI (2010-08-05). Liposomal co-encapsulation of quercetin with synergistic chemotherapeutic drugs for breast cancer treatment. ScholarBank@NUS Repository.
Abstract: Quercetin is a flavonoid commonly found in fruits and vegetables which exerts selective cytotoxicity on cancer cells and synergizes with chemotherapeutic drugs. However, its clinical usage has been hampered by low water solubility. Therefore, the objectives of this work were to (i) develop a liposomal formulation to solubilize quercetin, (ii) identify chemotherapeutic drugs that synergize with quercetin in breast cancer cells, (iii) co-encapsulate quercetin/drug combinations into liposomes, and (iv) evaluate the co-encapsulated formulation in vitro and in vivo. Liposomal encapsulation of quercetin was around 100%, increased its solubility by 10-fold, reduced quercetin degradation and the formulation was also physically stable. Quercetin synergized with (i) irinotecan and (ii) vincristine in the JIMT-1 and MDA-MB-231 breast cancer cell lines. Irinotecan could be encapsulated in DPPC/DSPE-PEG2000/Quercetin (90:5:5 mole ratio) liposomes with around 80% efficiency and vincristine could be encapsulated in ESM/Cholesterol/PEG2000-ceramide/Quercetin (72.5:17.5:5:5 mole ratio) liposomes with around 70% efficiency. Both formulations displayed controlled and co-ordinated release of the two agents. In vitro evaluation of liposomal vincristine/quercetin formulation comprising of ESM/Cholesterol/PEG2000-ceramide/Quercetin 72.5:17.5:5:5 mole ratio demonstrated the highest anti-cancer activity; thus, this formulation was further evaluated in vivo. Through liposomal co-encapsulation, plasma half lives of quercetin and vincristine were increased, and the synergistic ratio of the two drugs maintained. The formulation exhibited significant anti-tumor activity at two-thirds of the maximum tolerated dose of vincristine in a human epidermal growth factor 2 overexpressing, trastuzumab-resistant breast tumor xenograft model.
URI: http://scholarbank.nus.edu.sg/handle/10635/21061
Appears in Collections:Ph.D Theses (Open)

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