Comparison Between an Oral Sulfate Solution and a 2 L of Polyethylene Glycol/Ascorbic Acid as a Split Dose Bowel Preparation for Colonoscopy.

BACKGROUND/AIMS: This study aimed to compare the efficacy and tolerability of an oral sulfate solution (OSS) versus 2 L of polyethylene glycol/ascorbic acid (2L-PEG/Asc) for bowel cleansing before colonoscopy. METHODS: A prospective, single-center, single-blinded, noninferiority, randomized, controlled trial was performed. The primary outcome was the rate of successful bowel cleansing, evaluated using the Boston Bowel Preparation Scale (BBPS). Secondary outcomes were examination time, polyp, and adenoma detection rate (PDR and ADR), tolerability, and safety. Ease of use, palatability, intention to reuse, and satisfaction were evaluated using a questionnaire. RESULTS: A total of 187 participants were randomized to receive either OSS (n=93) or 2L-PEG/Asc (n=94). Successful bowel cleansing was achieved in 86.0% (80/93) of the OSS group, which was noninferior to the 2L-PEG/Asc group (88.3%, 83/94), with a difference of -2.3% by ITT analysis [95% confidence interval (CI) -12.0 to +7.4]. The withdrawal time of the OSS group was significantly shorter than that of the 2L-PEG/Asc group (11.8±5.2 vs. 14.3±8.5; P=0.016). Ease of use, palatability, intention to reuse, and satisfaction were similar between the 2 groups. Adverse events were also similar between the 2 groups. Mucosal erythema (4.3%) and aphthous lesions (2.1%) were found only in the 2L-PEG/Asc group. CONCLUSIONS: OSS was as effective as 2L-PEG/Asc for successful bowel cleansing and had acceptable tolerability. OSS is a promising and safe low-volume preparation alternative for colonoscopy. (Clinical trial registration number: NCT02761213.).

Gelatin-chlorin e6 conjugate for in vivo photodynamic therapy.

BACKGROUND: Improving the water solubility of hydrophobic photosensitizer and increasing its accumulation in tumor tissue are essential for in vivo photodynamic therapy (PDT). Considering commercialization or clinical application in future, it will be promising to achieve these purposes by developing new agents with simple and non-toxic structure. RESULTS: We conjugated multiple chlorin e6 (Ce6) molecules to gelatin polymer, synthesizing two types of gelatin-Ce6 conjugates with different amounts of Ce6: gelatin-Ce6-2 and gelatin-Ce6-8. The resulting conjugates remained soluble in aqueous solutions for a longer time than hydrophobic Ce6. The conjugates could generate singlet oxygen and kill tumor cells upon laser irradiation. After intravenous injection into SCC-7 tumor-bearing mice, gelatin-Ce6-2 showed prolonged blood circulation and highly increased accumulation in tumor tissue as observed in real-time imaging in vivo. After laser irradiation, gelatin-Ce6-2 suppressed tumor growth completely and enabled improved PDT compared to free Ce6 and gelatin-Ce6-8. CONCLUSIONS: This work demonstrates that a simple structure based on photosensitizer and gelatin can highly improve water solubility and stability. Superior tumor tissue accumulation and increased therapeutic efficacy of gelatin-Ce6 during in vivo PDT showed its high potential for clinical application.

Folate-modified PLGA nanoparticles for tumor-targeted delivery of pheophorbide a in vivo.

Targeted drug delivery has been an important issue for tumor therapy including photodynamic therapy (PDT). The purpose of our study is to increase the targeting efficiency of photosensitizer (PS) using folate-modified nanoparticles (NPs) to tumor site in vivo. Folate receptor is over-expressed on the surface of many human cancer cells. We prepared poly (lactic-co-glycolic acid) (PLGA) NPs containing pheophorbide a (Pba), a PS that is used in PDT and generates free radical for killing cancer cells. The surface of NPs was composed of phospholipids modified with polyethylene glycol (PEG) and folate (FA). The size of the resulting FA-PLGA-Pba NPs was about 200 nm in PBS at pH 7.4 and they were stable for long time. They showed faster cellular uptake to MKN28 human gastric cancer cell line than control PLGA-Pba NPs by high-affinity binding with folate receptors on cell surface. In MTT assay, FA-PLGA-Pba NPs also showed enhanced tumor cell killing compared to control PLGA-Pba NPs. In vivo and ex vivo imaging showed high accumulation of FA-PLGA-Pba NPs in tumor site during 24 h after intravenous injection to MKN28 tumor-bearing mice model. These results demonstrate that our FA-PLGA-Pba NPs are useful for tumor-targeted delivery of PS for cancer treatment by PDT.

The therapeutic effect of cyanoacrylate on gastric variceal bleeding and factors related to clinical outcome.

BACKGROUND: Cyanoacrylate has been recommended for the treatment of gastric variceal bleeding. GOAL: We aimed to evaluate the efficacy and safety of cyanoacrylate injection therapy in patients with gastric variceal bleeding, and to identify the factors predictive of failure, rebleeding, and survival after therapy. STUDY: One hundred twenty-one patients with gastric variceal bleeding who received cyanoacrylate injections were retrospectively reviewed. RESULTS: Treatment succeeded in 110 patients (90.9%). Rebleeding and mortality rate during 4-week were 13.2% and 11.6%. A stepwise logistic regression analysis indicated that only the Child-Pugh class was an independent predictive factor of treatment failure [Child-Pugh C vs. Child-Pugh A and B, odds ratio (OR), 5.0; 95% confidence interval (CI), 1.2-19.4; P=0.025]. The actuarial probability of a 4-week absence of rebleeding and survival after the initial therapy was 86.8% and 85.1%, respectively. A stepwise logistic regression analysis showed that a Child-Pugh class C and hepatocellular carcinoma were independent predictive factors for rebleeding (OR, 7.4; 95% CI, 2.0-27.0; P=0.003 and OR, 3.3; 95% CI, 1.0-11.1; P=0.05, respectively) and mortality (OR, 7.4; 95% CI, 2.0-27.0; P=0.003 and OR, 3.3; 95% CI, 1.0-11.1; P=0.05, respectively). Only 2 cases (2.7%) with serious complications, noted as cyanoacrylate embolisms, were observed. At 1-year follow up, the actuarial probability of remaining free of bleeding was 49.0% and hepatitis B virus infection was independent predictive factor of bleeding (OR, 5.3; 95% CI, 1.4-20.0; P=0.015). CONCLUSIONS: In short-term follow-up, cyanoacrylate injection is an effective treatment method for gastric variceal bleeding and the Child-Pugh class was only independent predictive factor of treatment failure and the Child-Pugh class and the hepatocellular carcinoma were risk factors for rebleeding and survival. In long-term follow-up, the presence of hepatitis B infection was risk factor for rebleeding.

Photodynamic Therapy Using Photosensitizer-Encapsulated Polymeric Nanoparticle to Overcome ATP-Binding Cassette Transporter Subfamily G2 Function in Pancreatic Cancer.

Chlorin-based photosensitizers are commonly used in photodynamic therapy (PDT). These drugs are effluxed by cell membrane transporters, such as the ATP-binding cassette subfamily G member 2 (ABCG2). PDT efficacy is limited in tumor cells expressing high levels of these proteins. Pancreatic cancer cell lines AsPC-1 and MIA PaCa-2, which have high and low ABCG2 expression, respectively, were used, and ABCG2-overexpressing MIA PaCa-2 cells were generated. We compared PDT efficacy between chlorin e6 (Ce6) and cationic photosensitizer-encapsulated polymeric nanoparticle (PS-pNP), which is comprised with Ce6, polyethylene glycol, and polyethylenimine. The intracellular concentration of Ce6 was significantly higher in MIA PaCa-2 cells than in AsPC-1 or ABCG2-overexpressing MIA PaCa-2 cells. PS-pNP increased intracellular levels of the photosensitizer in all cell lines. The cell viability experiments indicated increased Ce6 resistance in ABCG2-overexpressing cells. In contrast, PS-pNP produced similar levels of cytotoxicity in each of the cancer cell lines tested. Singlet oxygen production was higher in cells treated with PS-pNP than in those treated with Ce6. Furthermore, in heterotopic and orthotopic AsPC-1 xenograft mouse models, PDT using PS-pNP significantly reduced tumor volume in comparison with that of Ce6 treatment. PS-pNP could increase intracellular Ce6 concentration, which was related with reduced ABCG2-mediated efflux of Ce6, thereby enhancing the effects of PDT in pancreatic cancer cells. Mol Cancer Ther; 16(8); 1487-96. ©2017 AACR.

Photochemical tissue penetration via photosensitizer for effective drug penetration in a non-vascular tumor.

To improve the tissue penetration efficiency (PE%) of hydrophilic-drugs in non-vascular drug eluting stents (DES), we designed photochemical tissue penetration (PTP) invested DES (PTP-DES). The PTP technology was applied to the stent as a covering membrane to generate singlet oxygen. Singlet oxygen damages the epithelial layer, so the PE% of released drugs could be improved. To prepare the PTP-DES membrane, chlorin e6 (Ce6, photosensitizer) was incorporated in a gemcitabine (GEM) eluting polyurethane (PU) membrane (Ce6-GEM-PU). Ce6-GEM-PU has smooth surface that is ∼40 µm thick. The photoactivity of Ce6 was maintained for 2 weeks (in vitro GEM releasing period). In a separate cell culture system, both 1.5 folds higher PE% and an improved tumor cell growth inhibition effect were shown after light exposure. Additionally, in tissue penetration experimental system, 2 folds increased in the PE% of GEM was induced by laser exposure at 80 J/cm2. Additionally, improved PE% of hydrophilic molecules (Fluorescein and GEM) was confirmed in colon tumor bearing mice. Consequentially, tumor growth, when implanted with Ce6-GEM-PU, was effectively inhibited without significant side effects. Based on these results, we believe that the PTP-DES system has great potential for improving the therapeutic effect of conventional DES.