The key role of sulfation and branching on fucoidan antitumor activity

There is an urgent need for antitumor bioactive agents with minimal or no side effects over normal adjacent cells. Fucoidan is a marine-origin polymer with known antitumor activity. However, there are still some concerns about its application due to the inconsistent experimental results, specifically its toxicity over normal cells and the mechanism behind its action. Herein, three fucoidan extracts (FEs) have been tested over normal and breast cancer cell lines. From cytotoxicity results, only one of the extracts shows selective antitumor behavior (at 0.2 mg mLâ 1), despite similarities in sulfation degree and carbohydrates composition. Although the three FEs present different molecular weights, depolymerization of selected samples discarded Mw as the key factor in the antitumor activity. Significant differences in sulfates position and branching are observed, presenting FE 2 the higher branching degree. Based on all these experimental data, it is believed that these last two properties are the ones that influence the cytotoxic effects of fucoidan extracts.The authors would like to thank the funding from projects 0687_NOVOMAR_1_P, cofunded by INTERREG 2007-2013/POCTEP, CarbPol_u_Algae (EXPL/MAR-BIO/0165/2013), and IF/00376/2014/CP1212/CT0015, funded by the Portuguese Foundation for Science and Technology, FCT, and ComplexiTE (ERC-2012-ADG 20120216-321266), funded by the European Research Council under the European Union's Seventh Framework Programme for Research and Development. The authors would also like to thank FCT, Portugal, for the scholarship of A.S.F. (SFRH/BD/102471/2014), fellowship of C.N. (SFRH/BPD/100627/2014), Investigator grants of A.M. (IF/00376/2014), R.N.-C. (IF/00373/2014), and I.P. (IF/00032/2013) and the financial support to CICECO-Aveiro Institute of Materials (POCI-01-0145-FEDER-007679, FCT UID/CTM/50011/2013) and OOPNA (UID/OUI/00062/2013), through national founds and cofinanced by the FEDER, within the PT2020 Partnership Agreement

Colon-Specific Drug Delivery Behavior of pH-Responsive PMAA/Perlite Composite

The preparation, characterization, and in vitro release of 5-aminosalicylic acid (5-ASA) from methacrylic acid (MAA)/perlite composites (APC) prepared via a sol–gel route are reported. The free-radical graft polymerization of methacrylic acid (MAA) onto perlite particles was studied experimentally. The grafting procedure consisted of surface activation with 3-(trimethoxysilyl) propyl methacrylate (TSPA), followed by free-radical graft polymerization of methacrylic acid (MAA) in ethyl acetate with 2,2′-azobisisobutyronitrile (AIBN) initiator. The composition of the composites hybrid materials was determined by FTIR spectroscopy. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). The dried composites were immersed in a saturated solution of 5-ASA in water overnight and dried over a period of three days at room temperature and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4). The 5-ASA concentration of the solution was measured using a UV-Vis spectrophotometer (205 nm) at different time intervals. The in vitro drug release test revealed that the release rate of 5-ASA in buffer solutions increased with the silica content in the composites; on the contrary, the increase of the content of 3-(trimethoxysilyl)propyl methacrylate (TSPA), a coupling agent, decreased the drug release rate

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

BACKGROUND: Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. OBJECTIVES: We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. METHODS: A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. RESULTS: Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. CONCLUSION: Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system

Enzymatic Synthesis of Alkyds

AbstractThis paper describes the application of lipase-catalyzed polytransesterification to the preparation of two series of unsaturated “all trans” polyesters (alkyds): in the first series the starting materials were diesters of fumaric acid and 1,4-butane diol, and in the second, bischloroethyl fumarate and aromatic diols (benzene dimethanol and derivatives of bisphenol A). Most of the reactions were carried out in tetrahydrofuran and acetonitrile. As opposed to the extensive isomerization which occurs during the synthesis of unsaturated polyesters by chemical polycondensation, no isomerization of the double bond was found under the mild conditions of enzymatic catalysis. The “all trans” character of our alkyds was determined by nmr spectroscopy, and average molecular weights and dispersivity were measured by gel permeation chromatography. The average molecular weight was found to vary with the solvent. In acetonitrile a relatively high-melting point alkyd was obtained (m.p. 106–108°C), with low solubility in conventional solvents. Powder X-ray diffraction and SEM analyses revealed crystaUinity and layer-type structures.</jats:p