TY - JOUR TI - Application of emulsion-based delivery system to enhance bioavailability and efficacy of tangeretin DO - https://doi.org/doi:10.7282/T30V8FC2 PY - 2014 AB - Tangeretin (5,6,7,8,4′-pentamethoxyflavone) is a polymethoxylated flavone found predominantly in citrus fruit peels. Numerous bio-functionalities have previously been reported for tangeretin. For chronic intakes, oral ingestion is typically the preferred method since it is the most convenient and non-invasive application route. However, tangeretin exhibits poor oral bioavailability as a result of its hydrophobic chemical structure. Consequently, the required tangeretin oral dosage for many intended therapeutic purposes is difficult to achieve. In this work, we aim to use an emulsion-based delivery system to enhance the bioavailability and efficacy of tangeretin. In first part of this work, a viscoelastic emulsion system containing >2.5% tangeretin was developed and its physical properties were characterized. In this viscoelastic emulsion system, the emulsion-encapsulated tangeretin was mixed with homogeneously-entrapped tangeretin crystals, which exhibited remarkable storage stability over six months. Following the development of the tangeretin emulsion system, the processing parameters were further optimized to obtain the required properties that may best enhance the oral bioavailability and efficacy. The ability of an emulsion-based delivery system to improve the oral bioavailability of tangeretin was examined using in vitro and in vivo models. In vitro lipolysis and TNO gastrointestinal model revealed that emulsion-delivered tangeretin was digested considerably more quickly and was 2.6-fold more bioaccessible than unformulated medium-chain triglyceride (MCT) suspension. In vivo pharmacokinetics analysis on mice confirmed that the oral bioavailability of tangeretin in the emulsion-based system was increased 2.3-fold, with a 23% increase in Cmax when compared with the unformulated suspension. Moreover, the emulsion-based delivery was proven to be an effective method to increase the oral therapeutic efficacy of tangeretin. The in vitro anti-proliferative activity of tangeretin was first evaluated using MTT essay on colonic carcinoma cell lines and was significantly improved by the use of the emulsion delivery system. The effectiveness of the emulsion system to enhance the in vivo oral efficacy of tangeretin against colorectal cancer development was also evaluated by the AOM/DSS-induced colitis-related colon tumorigenesis model. The tumor incidence, multiplicity, and pathological signs of colorectal adenoma were significantly reduced when tangeretin emulsion was applied. Finally, the related toxicity effects of the tangeretin viscoelastic emulsion were also investigated. KW - Food Science KW - Drug delivery systems KW - Flavonoids LA - eng ER -