RIFM fragrance ingredient safety assessment, ethyl lactate, CAS registry number 97-64-3.

The existing information supports the use of this material as described in this safety assessment. Ethyl lactate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data on ethyl lactate show that ethyl lactate is not genotoxic and provided a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity, reproductive toxicity, and local respiratory endpoints. Data from ethyl lactate and additional material ethyl (L)-lactate (CAS # 687-47-8) show that there are no safety concerns for ethyl lactate for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; ethyl lactate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; ethyl lactate was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

Longitudinal assessment of ultrasound-guided complementary microRNA therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the second-leading cause of cancer related deaths worldwide and new strategies to efficiently treat HCC are critically needed. The aim of this study was to assess the longitudinal treatment effects of two complementary miRNAs (miRNA-122 and antimiR-21) encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA) - poly ethylene glycol (PEG) nanoparticles (PLGA-PEG-NPs), administered by an ultrasound-guided and microbubble-mediated delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts. Using in vitro assays, we show that repeated miRNA treatments resulted in gradual reduction of HCC cell proliferation and reversal of doxorubicin resistance. Optimized US parameters resulted in a 9-16 fold increase (p = 0.03) in miRNA delivery in vivo in HCC tumors after two US treatments compared to tumors without US treatment. Furthermore, when combined with doxorubicin (10 mg/kg), longitudinal miRNA delivery showed a significant inhibition of tumor growth in both resistant and non-resistant tumors compared to non-treated, and doxorubicin treated controls. We also found that ultrasound-guided miRNA therapy was not only effective in inhibiting HCC tumor growth but also allowed lowering the dose of doxorubicin needed to induce apoptosis. In conclusion, the results of this study suggest that ultrasound-guided and MB-mediated delivery of miRNA-122 and antimiR-21, when combined with doxorubicin, is a highly effective approach to treat resistant HCC while reducing doxorubicin doses needed for treating non-resistant HCC in longitudinal treatment experiments. Further refinement of this strategy could potentially lead to better treatment outcomes for patients with HCC.

Encapsulation of drug reservoirs in fibers by emulsion electrospinning: morphology characterization and preliminary release assessment.

In this paper, we prepared composite fibers via electrospinning from either W/O or O/W emulsion. SEM images demonstrate the beads-in-string structures in these fibers and proved this technique to be an effective method for microencapsulation. As a practical application, Ca-alginate microspheres, which serve as reservoirs for hydrophilic drugs, were prepared in a reverse emulsion and then incorporated into poly (l-lactic acid) (PLLA) fibers by electrospinning. With the bovine serum albumin (BSA) loaded into the microspheres, the beads-in-string structure thus entrapped hydrophilic proteins in hydrophobic polymeric matrix. In the in vitro release test, BSA, which was released from composite fibers, achieved prolonged release profiles and lower burst release rates than those from naked Ca-alginate microspheres. In comparison with other well-established techniques to prepare microcapsules, such as solvent evaporation and spray-drying techniques, emulsion electrospinning features partly competing, partly complementary characteristics. Extension to other emulsion systems will be able to fabricate new types of functional structures.

Quantitative assessment of the tissue response to implanted biomaterials.

The tissue response to a small number of polymeric biomaterials was studied using monoclonal antibodies specific for certain inflammatory cell types, to develop a reliable and accurate method for the quantitative evaluation of biocompatibility. The sites of antibody binding were identified using an avidin-biotin staining procedure and the sections evaluated using a computer-aided image analysis system. The staining technique successfully demonstrated both polymorphonuclear leucocytes and macrophages in tissue samples containing polymeric biomaterials. The image analysis system facilitated the measurement of up to 30 cell-related parameters and allowed a large number of cells to be analysed.