Cationic amphiphiles against Gardnerella vaginalis resistant strains and bacterial vaginosis-associated pathogens.

Antibiotic resistance and infection recurrence are critical issues in treating bacterial vaginosis, the most common vaginal disorder in women of reproductive age. Novel alternatives to traditional antibiotics, such as peptidomimetics, have the potential to address this challenge. Previously, two series of cationic amphiphiles (CAms) were developed with both hydrophilic head groups and non-polar domains, giving them the ability to self-assemble into supramolecular nanostructures with membrane-lytic properties.

Cationic Amphiphiles with Specificity against Gram-Positive and Gram-Negative Bacteria: Chemical Composition and Architecture Combat Bacterial Membranes.

Small-molecule cationic amphiphiles (CAms) were designed to combat the rapid rise in drug-resistant bacteria. CAms were designed to target and compromise the structural integrity of bacteria membranes, leading to cell rupture and death. Discrete structural features of CAms were varied, and structure-activity relationship studies were performed to guide the rational design of potent antimicrobials with desirable selectivity and cytocompatibility profiles.

Nanotherapeutics Containing Lithocholic Acid-Based Amphiphilic Scorpion-Like Macromolecules Reduce In Vitro Inflammation in Macrophages: Implications for Atherosclerosis.

Previously-designed amphiphilic scorpion-like macromolecule (AScM) nanoparticles (NPs) showed elevated potency to counteract oxidized low-density lipoprotein (oxLDL) uptake in atherosclerotic macrophages, but failed to ameliorate oxLDL-induced inflammation. We designed a new class of composite AScMs incorporating lithocholic acid (LCA), a natural agonist for the TGR5 receptor that is known to counteract atherosclerotic inflammation, with two complementary goals: to simultaneously decrease lipid uptake and inhibit pro-inflammatory cytokine secretion by macrophages. LCA was conjugated to AScMs for favorable interaction with TGR5 and was also hydrophobically modified to enable encapsulation in the core of AScM-based NPs.

Degree of Unsaturation and Backbone Orientation of Amphiphilic Macromolecules Influence Local Lipid Properties in Large Unilamellar Vesicles.

Liposomes have become increasingly common in the delivery of bioactive agents due to their ability to encapsulate hydrophobic and hydrophilic drugs with excellent biocompatibility. While commercial liposome formulations improve bioavailability of otherwise quickly eliminated or insoluble drugs, tailoring formulation properties for specific uses has become a focus of liposome research. Here, we report the design, synthesis, and characterization of two series of amphiphilic macromolecules (AMs), consisting of acylated polyol backbones conjugated to poly(ethylene glycol) (PEG) that can serve as the sole additives to stabilize and control hydrophilic molecule release rates from distearoylphosphatidylcholine (DSPC)-based liposomes.

Biodegradable Kojic Acid-Based Polymers: Controlled Delivery of Bioactives for Melanogenesis Inhibition.

Kojic acid (KA) is a naturally occurring fungal metabolite that is utilized as a skin-lightener and antibrowning agent owing to its potent tyrosinase inhibition activity. While efficacious, KA's inclination to undergo pH-mediated, thermal-, and photodegradation reduces its efficacy, necessitating stabilizing vehicles. To minimize degradation, poly(carbonate-esters) and polyesters comprised of KA and natural diacids were prepared via solution polymerization methods.

Spatial location of indomethacin associated with unimeric amphiphilic carrier macromolecules as determined by nuclear magnetic resonance spectroscopy.

A combination of nuclear magnetic resonance (NMR) techniques including, proton NMR, relaxation analysis, two-dimensional nuclear Overhauser effect spectroscopy, and diffusion-ordered spectroscopy, has been used to demonstrate the spatial location of indomethacin within a unimolecular micelle. Understanding the location of drugs within carrier molecules using such NMR techniques can facilitate rational carrier design. In addition, this information provides insight to encapsulation efficiency of different drugs to determine the most efficient system for a particular bioactive.

Designing polymers with sugar-based advantages for bioactive delivery applications.

Sugar-based polymers have been extensively explored as a means to increase drug delivery systems' biocompatibility and biodegradation. Here,we review he use of sugar-based polymers for drug delivery applications, with a particular focus on the utility of the sugar component(s) to provide benefits for drug targeting and stimuli responsive systems. Specifically, numerous synthetic methods have been developed to reliably modify naturally-occurring polysaccharides, conjugate sugar moieties to synthetic polymer scaffolds to generate glycopolymers, and utilize sugars as a multifunctional building block to develop sugar-linked polymers.

Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D.