Dimethyldioctadecylammonium bromide - CAS 3700-67-2

MicroRNAs (miRNAs) are non-coding endogenous RNAs that direct post-transcriptional regulation of gene expression by several mechanisms. Activity is primarily through binding to the 3' untranslated regions (UTRs) of messenger RNAs (mRNA) resulting in degradation and translation repression. Unlike other small-RNAs, miRNAs do not require perfect base pairing, and thus, can regulate a network of broad, yet specific, genes. Although we have only just begun to gain insights into the full range of biologic functions of miRNA, their involvement in the onset and progression of disease has generated significant interest for therapeutic development. Mounting evidence suggests that miRNA-based therapies, either restoring or repressing miRNAs expression and activity, hold great promise. However, despite the early promise and exciting potential, critical hurdles often involving delivery of miRNA-targeting agents remain to be overcome before transition to clinical applications. Limitations that may be overcome by delivery include, but are not limited to, poor in vivo stability, inappropriate biodistribution, disruption and saturation of endogenous RNA machinery, and untoward side effects. Both viral vectors and nonviral delivery systems can be developed to circumvent these challenges. Viral vectors are efficient delivery agents but toxicity and immunogenicity limit their clinical usage. Herein, we review the recent advances in the mechanisms and strategies of nonviral miRNA delivery systems and provide a perspective on the future of miRNA-based therapeutics.

In preparing polymer capsules by vesicle templated emulsion polymerization, the initial size and morphology of the biomimetic vesicle template dictate the final size and morphology of the capsules. The presence of salts (NaCl, NaBr and LiCl) influences the size, dispersity (PDI) and morphology of dimethyldioctadecylammonium bromide or chloride (DODAX, X = Br- or Cl-) vesicles, prepared via membrane extrusion. DODAX vesicles in pure water exhibit broad size distributions with PDI of 0.5 and 0.3 for DODAB and DODAC, respectively. Addition of salts in water before (pre-addition) and after (post-addition) extrusion reduces the size and PDI of the vesicles significantly and results in various morphology investigated with cryo-TEM. It is observed that at low salt concentration (≤0.5 mM) in pre-addition, DODAX exists as a nice quasi spherical unilamellar vesicle, suitable for vesicle templated polymerization whereas in post-addition of salt at any concentration, the morphology is dominated by structures not suitable for templating application. The information obtained here is crucial for vesicle templated emulsion polymerization and it will be shown that there is a relationship between vesicle template morphology and final polymer capsule morphology.

The meningococcal disease is a global health threat, but is preventable through vaccination. Adjuvants improve meningococcal vaccines and are able to trigger different aspects of the immune response. The present work evaluated the immune response of mice against Neisseria meningitidis outer membrane vesicles (OMV) complexed with the adjuvants aluminium hydroxide (AH), via subcutaneous route; and dimethyldioctadecylammonium bromide (DDA) or Saponin (Sap), via intranasal/subcutaneous routes. ELISA demonstrated that all adjuvants increased IgG titers after the booster dose, remaining elevated for 18 months. Additionally, adjuvants increased the avidity of the antibodies and the bactericidal titer: OMVs alone were bactericidal until 1: 4 dilution but, when adjuvanted by Alum, DDA or Sap, it increased to 1/32. DDA and Sap increased all IgG isotypes, while AH improved IgG1 and IgG2a levels. Thus, Sap led to the recognition of more proteins in Immunoblot, followed by DDA and AH. Sap and AH induced higher IL-4 and IL-17 release, respectively. The use of adjuvants improved both cellular and humoral immune response, however, each adjuvant contributed to particular parameters. This demonstrates the importance of studying different adjuvant options and their suitability to stimulate different immune mechanisms, modulating the immune response.