An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease.

There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD.

Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards.

There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify "signatures" for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes.

Adjunctive chemotherapeutic suppression of mutans streptococci in the setting of severe early childhood caries: an exploratory study.

OBJECTIVES: This investigational study assessed the suppressive effect of 10 percent povidone iodine (PI) coupled with elimination of active carious lesions on salivary mutans streptococci (MS) populations in children with severe early childhood caries (S-ECC). METHODS: 77 children (38 females, 39 males) were treated for S- ECC in one session; a 0.2 ml PI solution was applied to the dentition after dental surgery was completed and immediately wiped off. The subjects aged from 2 to 5 years (mean = 3.78 years) at baseline. Whole nonstimulated saliva samples were obtained at baseline, 30 days, 60 days, and 90 days post dental surgery. Samples were placed on ice and processed within 2 hours. The MS level in each sample was expressed as colony forming units (CFUs) per ml of saliva. RESULTS: Approximately 50 percent of subjects had a >95 percent reduction in CFU/ml of saliva at each time point after baseline. The percentages of subjects with a >50 percent reduction in MS level were 85 percent at 30 days, 83 percent at 60 days, 84 percent at 90 days. The median (25th, 75th percentiles) CFUs/ml of saliva counts were 8.40 x 10(5) (1.49 x 10(5), 5.00 x 10(6)) at baseline (n= 77), 4.12 x 10(4) (8.40 x 10(3), 1.89 x 10(5)) at 30 days (n = 74), 4.62 x 10(4) (7.00 x 10(3), 1.36 x 10(5)) at 60 days (n = 70), and 5.09 x 10(4) (1.16 x 10(4), 1.00 x 10(5)) at 90 days (n = 70). The changes from baseline to 30 days, 60 days, and 90 days were statistically significant (P < 0.0001). CONCLUSIONS: PI coupled with dental surgery has a significant suppressive effect on salivary MS levels in the setting of S-ECC for at least 90 days. These data strongly suggest that treatment with PI may be an important adjunct to dental surgery for S-ECC.