Strong Variation of Micelle-Unimer Coexistence as a Function of Core Chain Mobility.

Polymeric micelles coexist in solution with unassembled chains (unimers). We have investigated the influence of glass transition temperature ( ) (i.e.

Polymeric persulfide prodrugs: Mitigating oxidative stress through controlled delivery of reactive sulfur species.

Related biologically to the known gasotransmitter hydrogen sulfide (HS), persulfides (R-SSH) have recently been recognized as native signaling compounds and redox regulators in their own right. Reported here is the synthesis, characterization, and evaluation of a small molecule persulfide donor and its polymeric counterpart, both of which release -acetyl cysteine persulfide (NAC-SSH) in response to esterases. The donors, termed EDP-NAC and poly(EDP-NAC), underwent controlled decomposition in response to porcine liver esterase, resulting in pseudo-first-order release half-lives of 1.

Crescent-Shaped Supramolecular Tetrapeptide Nanostructures.

Self-assembly of amphiphilic peptide-based building blocks gives rise to a plethora of interesting nanostructures such as ribbons, fibers, and tubes. However, it remains a great challenge to employ peptide self-assembly to directly produce nanostructures with lower symmetry than these highly symmetric motifs. We report here our discovery that persistent and regular crescent nanostructures with a diameter of 28 ± 3 nm formed from a series of tetrapeptides with the general structure AdKKEX (Ad = adamantyl group, K = lysine residue functionalized with an -aroylthiooxime (SATO) group, E = glutamic acid residue, and X = variable amino acid residue).

Tuning small molecule release from polymer micelles: Varying HS release through cross linking in the micelle core.

Polymer micelles, used extensively as vehicles in the delivery of active pharmaceutical ingredients, represent a versatile polymer architecture in drug delivery systems. We hypothesized that degree of crosslinking in the hydrophobic core of amphiphilic block copolymer micelles could be used to tune the rate of release of the biological signaling gas (gasotransmitter) hydrogen sulfide (HS), a potential therapeutic. To test this hypothesis, we first synthesized amphiphilic block copolymers of the structure PEG--P(FBEA) (PEG = poly(ethylene glycol), FBEA = 2-(4-formylbenzoyloxy)ethyl acrylate).

The evolving landscape for cellular nitric oxide and hydrogen sulfide delivery systems: A new era of customized medications.

Nitric oxide (NO) and hydrogen sulfide (HS) are industrial toxins or pollutants; however, both are produced endogenously and have important biological roles in most mammalian tissues. The recognition that these gasotransmitters have a role in physiological and pathophysiological processes has presented opportunities to harness their intracellular effects either through inhibition of their production; or more commonly, through inducing their levels and or delivering them by various modalities. In this review article, we have focused on an array of NO and HS donors, their hybrids with other established classes of drugs, and the various engineered delivery platforms such a fibers, polymers, nanoparticles, hydrogels, and others.

The Benefits of Macromolecular/Supramolecular Approaches in Hydrogen Sulfide Delivery: A Review of Polymeric and Self-Assembled Hydrogen Sulfide Donors.

Cell homeostasis and redox balance are regulated in part by hydrogen sulfide (HS), a gaseous signaling molecule known as a gasotransmitter. Given its biological roles, HS has promising therapeutic potential, but controlled delivery of this reactive and hazardous gas is challenging due to its promiscuity, rapid diffusivity, and toxicity at high doses. Macromolecular and supramolecular drug delivery systems are vital for the effective delivery of many active pharmaceutical ingredients, and HS stands to benefit greatly from the tunable physical, chemical, and pharmacokinetic properties of polymeric and/or self-assembled drug delivery systems.

Tuning HS Release by Controlling Mobility in a Micelle Core.

Drug delivery from polymer micelles has been widely studied, but methods to precisely tune rates of drug release from micelles are limited. Here, the mobility of hydrophobic micelle cores was varied to tune the rate at which a covalently bound drug was released. This concept was applied to cysteine-triggered release of hydrogen sulfide (HS), a signaling gas with therapeutic potential.

A Persulfide Donor Responsive to Reactive Oxygen Species: Insights into Reactivity and Therapeutic Potential.

Persulfides (RSSH) have been hypothesized as critical components in sulfur-mediated redox cycles and as potential signaling compounds, similar to hydrogen sulfide (H S). Hindering the study of persulfides is a lack of persulfide-donor compounds with selective triggers that release discrete persulfide species. Reported here is the synthesis and characterization of a ROS-responsive (ROS=reactive oxygen species), self-immolative persulfide donor.