Where and how to find data on safety: what do systematic reviews of complementary therapies tell us?

Background: Successfully identifying relevant data for systematic reviews with a focus on safety may require retrieving information from a wider range of sources than for ‘effectiveness’ systematic reviews. Searching for safety data continues to prove a major challenge. Objectives: To examine search methods used in systematic reviews of safety and to investigate indexing. Methods: Systematic reviews focusing on safety of complementary therapies and related interventions were retrieved from comprehensive searches of major databases. Data was extracted on search strategies, sources used and indexing in major databases. Safety related search terms were compared against index terms available on major databases. Data extraction by one researcher using a pre-prepared template was checked for accuracy by a second researcher. Results: Screening of 2563 records resulted in 88 systematic reviews being identified. Information sources used varied with the type of intervention being addressed. Comparison of search terms with available index terms revealed additional potentially relevant terms that could be used in constructing search strategies. Seventy-nine reviews were indexed on PubMed, 84 on EMBASE, 21 on CINAHL, 15 on AMED, 6 on PsycINFO, 2 on BNI and HMIC. The mean number of generic safety-related indexing terms on PubMed records was 2.6. For EMBASE the mean number was 4.8 with at least 61 unique terms being employed. Most frequently used indexing terms and subheadings were adverse effects, side effects, drug interactions and herb-drug interactions. Use of terms specifically referring to safety varied across databases. Conclusions: Investigation of search methods revealed the range of information sources used, a list of which may prove a valuable resource for those planning to conduct systematic reviews of safety. The findings also indicated that there is potential to improve safety-related search strategies. Finally, an insight is provided into indexing of and most effective terms for finding safety studies on major databases.

Electrospun medicated shellac nanofibers for colon-targeted drug delivery

Medicated shellac nanofibers providing colon-specific sustained release were fabricated using coaxial electrospinning. A solution of 7.5 g shellac and 1.5 g of ferulic acid (FA) in 10 mL ethanol was used as the core fluid, and a mixture of ethanol and N,N-dimethylformamide (8/10 v/v) as the shell. The presence of the shell fluid was required to prevent frequent clogging of the spinneret. The diameters of the fibers (D) can be manipulated by varying the ratio of shell to core flow rates (F), according to the equation D = 0.52F−0.19. Scanning electron microscopy images revealed that fibers prepared with F values of 0.1 and 0.25 had linear morphologies with smooth surfaces, but when the shell fluid flow rate was increased to 0.5 the fiber integrity was compromised. FA was found to be amorphously distributed in the fibers on the basis of X-ray diffraction and differential scanning calorimetry results. This can be attributed to good compatibility between the drug and carrier: IR spectra indicated the presence of hydrogen bonds between the two. In vitro dissolution tests demonstrated that there was minimal FA release at pH 2.0, and sustained release in a neutral dissolution medium. The latter occurred through an erosion mechanism. During the dissolution processes, the shellac fibers were gradually converted into nanoparticles as the FA was freed into solution, and ultimately completely dissolved.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.

OBJECTIVE: The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. DESIGN: To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. RESULTS: Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. CONCLUSIONS: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.

Electrospun Contrast Agent-Loaded Fibers for Colon-Targeted MRI

Magnetic resonance imaging is a diagnostic tool used for detecting abnormal organs and tissues, often using Gd(III) complexes as contrast-enhancing agents. In this work, core–shell polymer fibers have been prepared using coaxial electrospinning, with the intent of delivering gadolinium (III) diethylenetriaminepentaacetate hydrate (Gd(DTPA)) selectively to the colon. The fibers comprise a poly(ethylene oxide) (PEO) core loaded with Gd(DTPA), and a Eudragit S100 shell. They are homogeneous, with distinct core–shell phases. The components in the fibers are dispersed in an amorphous fashion. The proton relaxivities of Gd(DTPA) are preserved after electrospinning. To permit easy visualization of the release of the active ingredient from the fibers, analogous materials are prepared loaded with the dye rhodamine B. Very little release is seen in a pH 1.0 buffer, while sustained release is seen at pH 7.4. The fibers thus have the potential to selectively deliver Gd(DTPA) to the colon. Mucoadhesion studies reveal there are strong adhesive forces between porcine colon mucosa and PEO from the core, and the dye-loaded fibers can be successfully used to image the porcine colon wall. The electrospun core–shell fibers prepared in this work can thus be developed as advanced functional materials for effective imaging of colonic abnormalities.