Pharmaceutical formulations (nanococktails) include two or more nanoparticulate delivery vehicles each including an active agent. The nanococktails can be formulated at any ratio of active agents by changing the ratio of nanoparticulate delivery vehicles in the nanococktail. The nanoparticulate delivery vehicles can have matched surface potential to prevent aggregation. The nanoparticulate delivery vehicles of the combined formulation are designed to provide each active agent with desired, preferably overlapping therapeutic windows and a specifically selected pharmacokinetic and pharmacodynamic profile when the nanococktail is administered to a subject. Each of the nanoparticulate delivery vehicles can be designed to enhance solubility, duration of action, targeting, stability, and to program release while preventing degradation of an active agent and preventing side effects, toxicity, and tolerability issues in a subject.

The presently disclosed subject matter describes the use of fluorinated elastomer-based materials, in particular perfluoropolyether (PFPE)-based materials, in high-resolution soft or imprint lithographic applications, such as micro- and nanoscale replica molding, and the first nano-contact molding of organic materials to generate high fidelity features using an elastomeric mold. Accordingly, the presently disclosed subject matter describes a method for producing free-standing, isolated nanostructures of any shape using soft or imprint lithography technique.

This invention relates, at least in part, to osmotic mediated release barrier-free synthetic nanocarriers and methods of production and use.

In various embodiments novel biodegradable acid-activated acid releasing nanoparticles (acNPs) are provided that are used as a targeted strategy to manipulate lysosomal acidity and autophagy. These acNPs based, in certain embodiments, on fluorinated polyesters are degraded at pH 6.0 (pH reported in dysfunctional lysosomes), and release component acids that further lower the lysosomal pH, and thereby increasing autophagic flux and cellular function of hepatocytes under LT. The acNPs can serve as a therapeutic in restoring liver-diseases.

Disclosed are pharmaceutical compositions including a plurality of nanoparticles including a compound of the following structure (1) or a pharmaceutically acceptable salt thereof. Also disclosed are methods of their use and preparation.

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Embodiments of the present invention are directed to dosage forms for treating inflammation and rejection in transplantation injuries, graft versus host disease and stem cell transplants with Bryostatin-1, Bryostatin-1 analogs and pharmaceutically acceptable salts thereof.

Nanoparticles include a polymeric core and a high density lipoprotein (HDL) component where the ratio by weight of the HDL component to the polymeric core is in a range from about 1:9 to about 9:1, such as about 75:25 or less or about 7:3 or less. The nanoparticles may also include a mitochondria targeting moiety. The nanoparticles may be used to treat or prevent atherosclerosis or to maintain lipid homeostasis.

The present disclosure provides nanoparticle compositions comprising i) a polymeric nanoparticle, ii) one or more ligands conjugated to the polymeric nanoparticle, and iii) naloxone. The disclosure also provides methods and pharmaceutical compositions comprising the nanoparticle compositions for use in treating patients with various disease states.

The method of treating obesity-induced glucose intolerance and liver fibrosis includes administering to a patient a therapeutically effective amount of a substance for inhibiting the Notch signaling pathway of the patient. The substance is formed from encapsulated γ-secretase inhibitor (GSI) nanoparticles. As a non-limiting example, each nanoparticle may be formed from a GSI, such as dibenzazepine (a bioavailable GSI) encapsulated in poly(lactic co-glycolic acid) (PLGA). The encapsulated GSI nanoparticles (GSI NPs) provide localized and effective inhibition of hepatic Notch signaling, thus improving obesity-induced glucose tolerance and liver fibrosis without intestinal side effects.

Disclosed are peptides that specifically bind to neutrophils and uses thereof for neutrophil-targeted delivery of drugs or diagnostic agents in medical conditions including cancer as well as infectious, inflammatory and autoimmune diseases or disorders.