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Through technological advancements, medical devices have evolved in their designs and have become more complex in both their design and materials of construction. Medical grade biocompatible epoxies are widely used in reusable medical devices. Choosing an epoxy that maintains its performance characteristics when subjected to repeated sterilization throughout the reusable medical device’s lifespan is a known challenge for medical device manufacturers. This study evaluated the material compatibility of seven cured 2-part and 1-part epoxies used in medical devices following exposure to 100 cycles in a low temperature vaporized hydrogen peroxide sterilizer. Six of the seven epoxies tested were found to be compatible with vaporized hydrogen peroxide sterilization based on qualitative, hardness and weight measurements conducted post exposure to 100 VHP cycles. The epoxies deemed to be compatible displayed no visual signs of physical defects, minimal reduction in hardness (≤2%) and total weight gain (≤2.9%). One of the epoxy samples did not maintain its texture and exhibited 17% loss in hardness post exposure to 100 VHP sterilization cycles and was found to be incompatible with the low temperature vaporized hydrogen peroxide process. This study verifies the need for material compatibility evaluations of epoxies prior to designing and developing a medical device while keeping in mind the application, lifecycle and intended use of medical devices. [ABSTRACT FROM AUTHOR]

We report a series of lipidated α-AApeptides that mimic the structure and function of natural antimicrobial lipopeptides. Several short lipidated α-AApeptides show broad-spectrum activity against a range of clinically related Gram-positive and Gram-negative bacteria as well as fungus. Their antimicrobial activity and selectivity are comparable or even superior to the clinical candidate pexiganan as well as previously reported linear α-AApeptides. The further development of lipidated α-AApeptides will lead to a new class of antibiotics to combat drug resistance.

There is increasing demand to develop antimicrobial peptides(AMPs)as next generation antibiotic agents, as they have the potential tocircumvent emerging drug resistance against conventional antibiotictreatments. Non-natural antimicrobial peptidomimetics are an idealexample of this, as they have significant potency and in vivo stability.Here we report for the first time the design of lipidated γ-AApeptidesas antimicrobial agents. These lipo-γ-AApeptides show potentbroad-spectrum activities against fungi and a series of Gram-positiveand Gram-negative bacteria, including clinically relevant pathogensthat are resistant to most antibiotics. We have analyzed their structure–functionrelationship and antimicrobial mechanisms using membrane depolarizationand fluorescent microscopy assays. Introduction of unsaturated lipidchain significantly decreases hemolytic activity and thereby increasesthe selectivity. Furthermore, a representative lipo-γ-AApeptidedid not induce drug resistance in S. aureus, evenafter 17 rounds of passaging. These results suggest that the lipo-γ-AApeptideshave bactericidal mechanisms analogous to those of AMPs and have strongpotential as a new class of novel antibiotic therapeutics. [ABSTRACT FROM AUTHOR]

Background/aim: One of the major hurdles in the treatment of breast cancers is the inability of anti-cancer drugs to eliminate the breast cancer stem cells (BCSCs) population, which leads to disease relapse. The dearth in anti-cancer drugs that target BCSCs can be attributed to the absence of in vitro screening models that can not only recapitulate the tumor microenvironment consisting of BCSCs but also preserve the 3-dimensional (3D) architecture of in vivo tumors., Materials and Methods: In our present study, we have developed a 3D cell culture system that shows: (i) enrichment of BCSCs, (ii) increased drug resistance, and (iii) generation of hypoxic conditions similar to tumors., Results: Using this model, we were able to screen a FDA-approved diversity set and identify as well as validate actinomycin D as a potential anti-breast cancer agent. Interestingly, we show that actinomycin D specifically targets and down-regulates the expression of the stem cell transcription factor, Sox-2. Additionally, down-regulation of Sox-2 leads to depletion of the stem-cell population resulting in the inability of breast cancer cells to initiate tumor progression., Conclusion: This study demonstrates the utility of an in vivo-like 3D cell culture system for the identification and validation of anti-cancer agents that will have a better probability of success in the clinic., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Herein we describe the development of a new class of antimicrobial and anti-inflammatory peptidomimetics: cyclic lipo-α-AApeptides. They have potent and broad-spectrum antibacterial activity against a range of clinically relevant pathogens, including both multidrug-resistant Gram-positive and Gram-negative bacteria. Fluorescence microscopy suggests that cyclic lipo-α-AApeptides kill bacteria by disrupting bacterial membranes, possibly through a mechanism similar to that of cationic host-defense peptides (HDPs). Furthermore, the cyclic lipo-α-AApeptide can mimic cationic host-defense peptides by antagonizing Toll-like receptor 4 (TLR4) signaling responses and suppressing proinflammatory cytokines such as tumor necrosis factor-α (TNF-α). Our results suggest that by mimicking HDPs, cyclic lipo-α-AApeptides could emerge as a new class of antibiotic agents that directly kill bacteria, as well as novel antiinflammatory agents that act through immunomodulation.

Some short and cationic peptides such as the Tat peptide can cross the cell membrane and function as vectors for intracellular delivery. Here we show that an α-AApeptide is able to penetrate the membranes of living cells from an extracellular environment and enter the endosome and cytoplasm of cells. The efficiency of the cellular uptake is comparable to a Tat peptide (48-57) of the same length and is unexpectedly superior to an α-peptide with identical functional groups. The mechanism of uptake is similar to that of the Tat peptide and is through endocytosis by an energy-dependent pathway. Due to the easy synthesis of the α-AApeptides, their resistance to proteolytic hydrolysis, and their low cytotoxicity, α-AApeptides represent a new class of transporters for the delivery of drugs.