Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer.

PURPOSE: The aim of the present study was to develop an optimized Genkwanin (GKA)-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation to enhance the solubility, intestinal permeability, oral bioavailability and anti-colitis-associated colorectal cancer (CAC) activity of GKA. METHODS: We designed a SNEDDS comprised oil phase, surfactants and co-surfactants for oral administration of GKA, the best of which were selected by investigating the saturation solubility, constructing pseudo-ternary phase diagrams, followed by optimizing thermodynamic stability, emulsification efficacy, self-nanoemulsification time, droplet size, transmission electron microscopy (TEM), drug release and intestinal permeability. In addition, the physicochemical properties and pharmacokinetics of GKA-SNEDDS were characterized, and its anti-colitis-associated colorectal cancer (CAC) activity and potential mechanisms were evaluated in AOM/DSS-induced C57BL/6J mice model. RESULTS: The optimized nanoemulsion formula (OF) consists of Maisine CC, Labrasol ALF and Transcutol HP in a weight ratio of 20:60:20 (w/w/w), in which ratio the OF shows multiple improvements, specifically small mean droplet size, excellent stability, fast release properties as well as enhanced solubility and permeability. Pharmacokinetic studies demonstrated that compared with GKA suspension, the relative bioavailability of GKA-SNEDDS was increased by 353.28%. Moreover, GKA-SNEDDS not only significantly prevents weight loss and improves disease activity index (DAI) but also reduces the histological scores of inflammatory cytokine levels as well as inhibiting the formation of colon tumors via inducing tumor cell apoptosis in the AOM/DSS-induced CAC mice model. CONCLUSION: Our results show that the developed GKA-SNEDDS exhibited enhanced oral bioavailability and excellent anti-CAC efficacy. In summary, GKA-SNEDDS, using lipid nanoparticles as the drug delivery carrier, can be applied as a potential drug delivery system for improving the clinical application of GKA.

Effects of duration of wearing high-heeled shoes on plantar pressure.

In the present study we investigated the effects of different durations of using high-heeled shoes on plantar pressure and gait. A questionnaire survey and dynamic plantar pressure measurements were performed in 20 control females and 117 females who had worn high-heeled shoes for a long time. According to the duration of using high-heeled shoes (as specified in the questionnaire), subjects were divided into a control group and five groups with different durations of use (i.e. <2years, 2-5years, 6-10years, 11-20years and >20years). Parameters, including peak pressure, impulse and pressure duration, in different plantar regions were measured with the Footscan pressure plate. The 2-5years group had smaller midfoot contact areas for both feet and higher subtalar joint mobility, while the 6-10years group had larger midfoot contact areas for both feet and prolonged foot flat phase during gait. The peak pressure and impulse under the second and fourth metatarsus were increased with the prolonged wearing of high-heeled shoes, and the pressure and impulse under the midfoot were substantially reduced in the 2-5years group. The findings suggest that long-term use of high-heeled shoes can induce changes in arch morphology: the longitudinal arch tends to be elevated within 2-5years; the longitudinal arch tends to be flattened within 6-10years; and the forefoot latitudinal arch tends to collapse in more than 20years.