methylcellulose and Colorectal-Neoplasms

Albendazole (ABZ) is a microtubule depolymerizing agent with a remarkable activity against a variety of tumor cells in vitro and in vivo. However, the lack of water solubility limits its application. Therefore, the aim of this study was to formulate ABZ with acetic acid/2-hydroxypropyl-β-cyclodextrin (HPβCD) with the view of improving its aqueous solubility and therefore, its antitumor efficacy.. ABZ was dissolved in acetic acid and 25% HPβCD (w/v). Mice received a single dose of ABZ/HPβCD or a conventional suspension in hydroxypropyl methyl cellulose (HPMC) over 24 h and the concentration of ABZ and its metabolites in plasma were measured by HPLC. The antitumor efficacy of the two formulations were then evaluated and compared in nude mice bearing HCT-116 colorectal cancer xenografts.. Ionization with acetic acid together with complexation with hydroxylpropyl-β-cyclodextrin (HPβCD) dramatically improved the solubility of ABZ. The area under the curve (AUC) of ABZ and its active metabolite, ABZ sulfoxide (ABZSO) were approximately 2.3- and 7.3-folds higher in mice that received ABZ/HPβCD in comparison with animals that were treated with ABZ/HPMC. Additionally, the peak plasma concentration (C(max)) of ABZSO was nearly 18-times higher in mice that received ABZ/HPβCD. Furthermore, a significant delay in tumor growth that led to longer survival in mice was observed in the ABZ/HPβCD-treated group as compared to the ABZ/HPMC group.. These findings demonstrate that the combination of acetic acid and HPβCD significantly improves the solubility, pharmacokinetic profile and antitumor efficacy of ABZ. This newly-developed formulation of ABZ may be suitable for parenteral administration.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acetic Acid; Albendazole; Animals; beta-Cyclodextrins; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Female; HCT116 Cells; Human Umbilical Vein Endothelial Cells; Humans; Hypromellose Derivatives; Injections, Intraperitoneal; Methylcellulose; Mice; Mice, Nude; Solutions; Suspensions; Tubulin Modulators; Xenograft Model Antitumor Assays

Compression coating is one of the approaches for delaying the release of drugs. The aim of this study was to develop colon-specific compression coated systems of 5-fluorouracil (5-FU) for the treatment of colorectal cancer using xanthan gum, boswellia gum and hydroxypropyl methylcellulose (HPMC) as the coating materials. Core tablets containing 50 mg of 5-FU were prepared by direct compression. The coating of the core tablets was done using different coat weights (230, 250, 275 and 300 mg) and different ratios (1:2, 2:1, 1:3, 1:7 and 3:4) of boswellia gum and xanthan gum and different ratios (1:1, 1:2, 2:1, and 2:3) of boswellia gum and HPMC. In-vitro release studies were carried out using simulated gastric and intestinal fluids, with and without rat caecal contents. Among the different ratios used for coating with boswellia:xanthan gum combination, ratio 1:3 gave the best release profile with the lowest coating weights of 230 mg (7.47 +/- 1.56% in initial 5 h). Further increase in the coat weights to 250, 275 and 300 mg led to drug release of 5.63 +/- 0.53%, 5.09 +/- 1.56% and 4.57 +/- 0.88%, respectively, in the initial 5 h and 96.90 +/- 0.66%, 85.05 +/- 1.01% and 80.22 +/- 0.35%, respectively, in 24 h. When coating was carried out using different ratios of the combination boswellia gum and HPMC, the ratio 2:3 gave the best results among the initial trial batches (7.80 +/- 0.57% in 5 h). Increasing the coat weights to 250, 275 and 300 mg led to drug release of 6.5 +/- 0.27%, 3.70 +/- 2.3% and 2.99 +/- 0.72%, respectively, in the initial 5 h and 96.90 +/- 0.66%, 85.05 +/- 1.01% and 80.22 +/- 0.35%, respectively, in 24 h. In-vitro studies were further carried out in the presence of 2% w/v rat caecal contents, which led to complete release of the drug from the tablets. Therefore, this study lays a basis for use of compression coating of 5-FU as a tool for delaying the release of the drug, which ensures better clinical management of the disease.

Topics: Animals; Antimetabolites, Antineoplastic; Boswellia; Chemistry, Pharmaceutical; Colon; Colorectal Neoplasms; Delayed-Action Preparations; Drug Delivery Systems; Excipients; Fluorouracil; Hypromellose Derivatives; In Vitro Techniques; Methylcellulose; Polysaccharides, Bacterial; Pressure; Rats; Tablets, Enteric-Coated

Assessment of 3 different rectal contrast agents (water, methylcellulose, ultrasound gel) for their suitability for colorectal imaging in multislice CT (MS-CT).. 115 patients with colorectal diseases underwent MS-CT with varying, rectal contrast agents in a prospective study. Images were assessed by 2 independent CT-experienced radiologists. 6 criterias were evaluated, using a 5-point scale.. Methylcellulose (MC) proved to be significantly superior to ultrasound gel (US). Especially, differentiation of healthy and diseased bowel and bowel wall and lumen were aided, which was proven by quantitative analysis of attenuation values. Rectal distension is greater using MC or US than for water. More proximal parts of the colon could be better distended with water. The interobserver correlation was good (kappa 0.76).. Rectal filling with MC significantly improves diagnostic confidence in colorectal examinations. Ease of administration and lack of problems suggest its use as a clinical routine tool.

Topics: Adult; Aged; Aged, 80 and over; Colitis, Ulcerative; Colonic Diseases; Colorectal Neoplasms; Contrast Media; Crohn Disease; Female; Gels; Humans; Male; Methylcellulose; Middle Aged; Observer Variation; Prospective Studies; Radiography, Abdominal; Rectal Diseases; Tomography, X-Ray Computed; Water

Evaluation as to whether diagnosis of large bowel disease and TNM staging of colorectal carcinoma are possible by colorectal hydrosonography (HUS).. 52 patients with suspected neoplastic or inflammatory large bowel disease, underwent HUS. Before performing abdominal ultrasound, the colon was filled with fluid. Morphological alterations of the bowel wall were judged benign or malignant. Colorectal carcinomas were classified according to the TNM system.. Laparotomy was performed in 46 of 52 patients. Correlation with surgery and histopathology showed that 77% of morphologic alterations of the colonic wall were detected by HUS. While benign lesions of the colonic wall occasionally mimicked malignant disease, colonic carcinomas were reliably diagnosed by HUS, because destruction and invasion of the bowel wall was visible. Carcinomas of the lower part of the rectum, however, were missed in most cases. Accuracy to determine the infiltration depth of colorectal carcinomas was 89%, but hydrosonographic N-staging was unreliable. Inflammatory disease of the large bowel as well as changes complicating the inflammatory bowel disease were accurately diagnosed by HUS.. In selected patients, colorectal HUS is suited for diagnosis and staging of colonic tumours. It also helps to evaluate inflammatory bowel disease, because small and large bowel can be reliably distinguished from each other and the degree of stenosis of inflamed colonic segments becomes visible. Furthermore, HUS increases the visibility of fistulas.

Topics: Colon; Colorectal Neoplasms; Contrast Media; Female; Humans; Inflammatory Bowel Diseases; Male; Methylcellulose; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Rectum; Ultrasonography

Insulin-like growth factors (IGFs) are potent proliferation stimulators for numerous tumor cells and often function as autocrine growth factors. We have previously shown that exogenous IGF-I and IGF-II enhance proliferation of colorectal carcinoma cells. The biological signal of both factors is transmitted through the IGF-I receptor (IGF-I-R). This receptor was expressed in 12/12 colorectal carcinoma cell lines tested. alpha IR3, a neutralizing monoclonal antibody (MAb) directed against the human IGF-I-R, inhibited proliferation in 7/12 lines (Caco-2, HT-29, LS411N, LS513, LS1034, WiDr and SW620), as reflected by a reduction of MTT conversion (19 to 42%), a decrease in cell number (39 to 72%) and an increase in doubling time (up to 2-fold). In addition, in 4 cell lines (Caco-2, LS513, LS1034, WiDr) alpha IR3 suppressed colony formation in methylcellulose (40 to 84%). Excess of exogenous IGF completely neutralized alpha IR3-mediated inhibitory effects. Northern blot analysis revealed abundant expression of 2 IGF-II transcripts of 5.0 and 4.3 kb in LS1034 cells. In addition, we observed that growth inhibition by alpha IR3 was correlated with a more differentiated phenotype. Our results suggest that growth of many colorectal carcinoma cell lines is regulated by autocrine IGF-II-mediated stimulation of the IGF-I-R.

Topics: Antibodies, Monoclonal; Blotting, Northern; Cell Adhesion; Cell Division; Colorectal Neoplasms; Culture Media; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Methylcellulose; Neoplastic Stem Cells; Receptor, IGF Type 1; Tumor Cells, Cultured