The inhibitory effects of novel prodrugs, inclusion complexes of 3-(4 0 -geranyloxy-3 0 -methoxyphenyl)-2-trans propenoic acid (GOFA) and auraptene (AUR) with b-cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/ dextran sodium sulfate (DSS) model. Male CD-1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/b-CD or AUR/b-CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/b-CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 6 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/b-CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/b-CD and AUR/b-CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor-kappaB, tumor necrosis factor-a, Stat3, NF-E2-related factor 2, interleukin (IL)-6 and IL-1b, which were induced in the adenocarcinomas. Our findings indicate that GOFA/b-CD and AUR/b-CD, especially GOFA/b-CD, are therefore able to inhibit colitis-related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.There were $1 million new cases of colorectal cancer (CRC) in 2002 (9.4% of the total cancers). 1 Globally, the mortality of CRC was reported to be 655,000 deaths per year in 2005. 2 There is at least a 25-fold variation in the occurrence of CRC worldwide.1 The highest rates of incidence are in North America, Australia/New Zealand, Western Europe and Japan, especially in Japanese men.1 These large geographic differences for CRC are probably explained by differences in environmental exposures and lifestyles.There are several types of pathogenesis of CRC. 3 Among them, inflammation is linked with CRC development. 4 The risk of CRC in patients with inflammatory bowel disease inflammatory bowel disease; IL: interleukin; iNOS: inducible nitric oxide synthase; NF-jB: nuclear factor-kappaB; Nrf2: NF-E2-related factor 2; TdT: terminal deoxynucleotidyl transferase; Tnf: tumor necrosis factor;

Aqueous solution diffusion coefficients for G0-G3 PAMAM dendrimers were determined from DOSY-NMR spectroscopy at high and neutral pH. The study was performed in a dilute regime and diffusion coefficients at infinite dilution (D 0 ) were estimated from the variation of diffusion coefficients with dendrimer concentration. Hydrodynamic radii (R h ) for each dendrimer were estimated from D 0 using the Stoke-Einstein relationship at both pH. According to D 0 and R h values, the structure of G0-G1 PAMAM dendrimers is almost insensitive to pH variations, whereas G2-G3 PAMAM dendrimers undergo swelling at neutral pH, due to surface amino groups protonation. Experimental diffusion coefficients show a scaling trend with the number of dendrimer atoms (N), with scaling laws of the type D 0 / N a , where a takes values of -0.39 and -0.50 at pH 12 and 7, respectively. For the first time, experimental data accounts for the scaling behavior of aqueous diffusion coefficients for low generation PAMAM dendrimers, as previously reported from molecular dynamics simulations.

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Complexation between acyclovir (ACV), an antiviral drug used for the treatment of herpes simplex virus infection, and beta-cyclodextrin (beta-CD) was studied in solution and in solid states. Complexation in solution was evaluated using solubility studies and nuclear magnetic resonance spectroscopy (¹H-NMR). In the solid state, X-ray diffraction, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and dissolution studies were used. Solubility studies suggested the existence of a 1:1 complex between ACV and beta-CD. ¹H-NMR spectroscopy studies showed that the complex formed occurs with a stoichiometry ratio of 1:1. Powder X-ray diffraction indicated that ACV exists in a semicrystalline state in the complexed form with beta-CD. DSC studies showed the existence of a complex of ACV with beta-CD. The TGA studies confirmed the DSC results of the complex. Solubility of ACV in solid complexes was studied by the dissolution method and it was found to be much more soluble than the uncomplexed drug