The Penn State Research Foundation

Other

Case Western Reserve University

University of Virginia Patent Foundation

University of Missouri

Mark Kester

James H Adair

Jill P Smith

Eric Pearlman

Gail L Matters

Thomas Stover

Tao Lowe

Thomas T Morgan

Young Shin Kim

Sriram S Shanmugavelandy

Erhan I Altinoglu

Brian M Barth

Peter C Eklund

William Benjamin White

Joseph Thomas Frank

Carlo Pantano

Ameer Hamza Shakeel

Sepehr Zomorodi

Payam Pourtaheri

John F Harms

Zachery George Davis

Todd Fox

Shaun Moshasha

Alan J Snyder

Kent E Vrana

Timothy J Russin

Christopher A Siedlecki

Kari Eyer

James M D Kaiser

Jeff Davidson

Jun Wang

Sarah M Rouse

Andrei Khokhlachev

Erwin Vogler

Victor Ruiz-Velasco

Lawrence Sinoway

Ugur Salli

Kevin Staveley-O'Carroll

Guangfu Li

Karam El-Bayoumy

Carlo G Pantano

Jeremy Shaw

Christine Skibinski

Rahul Sharma

Arunangshu Das

Pedro Filipe Da Costa Pinheiro

Mylisa Parette

James M Kaiser

Danielle Asquino

Christopher McGovern

Alan Snyder

Christopher Siedlecki

Victor Hershey Medical Center Ruiz-Velasco

Provided are methods for treating cancers and/or tumors in subjects. In some embodiments, the methods include administering to a subject an effective amount of a ceramide nanoliposome (CNL), wherein the CNL has a lipid bilayer that includes one or more C-Cceramides and encapsulates one or more anti-cancer and/or anti-tumor agents. Also provided are methods for treating cancers and/or tumors associated with receptor tyrosine kinase or nuclear receptor activities, methods for treating Prostate Cancer, methods for inhibiting growth of EGFR-dependent cancers and/or tumors, methods for inhibiting growth of androgen receptor negative cells, method for reducing or eliminating androgen receptor negative cells from subject, CNLs that encapsulate one or more anti-cancer and/or anti-tumor agents, wherein the CNLs include a lipid bilayer that has one or more C-Cceramides, and pharmaceutical compositions that include the disclosed CNLs.

Compositions and methods for cancer treatment

Methods and compositions for treating cancer are provided. Compositions comprising ceramide nanoliposomes are administered to a subject in need of such treatment. The composition administration also enhances immunotherapy. Further administering compositions in combination with tumor antigen specific T-cells, and/or compositions in combination with tumor antigen expressing cells, and/or said compositions in combination with antagonists of PD-1 provides for enhanced results. Administration of the compositions provides for effective treatment of tumors including regression and eradication of established tumors.

Ceramide nanoliposomes, compositions and methods of using for immunotherapy

Compositions and methods related to anucelate cells (e.g., bacterial minicells) for pesticide degradation applications including related cells, polypeptides, and vectors.

Compositions and methods for pesticide degradation

A method for treating and preventing diseases associated with neutrophil infiltration, particularly ocular diseases, is provided, which method comprises administering to a subject in need thereof an effective amount of ceramide or a derivative thereof. Also provided is a composition for treating diseases associated with neutrophil infiltration, the composition comprising ceramide or a derivative thereof.

Ceramide composition and method of use

The present invention relates to a liposomal formulation for oral delivery of a bioactive agent that considers pH stability and oxidative stability of a bioactive ingredient. These lipid formulations are superior to conventional liposomes due to their stability, thereby circumventing the need for intra-venous delivery of bioactive agents. In one embodiment, the methods and compositions of the present invention relate to the oral delivery of insulin or a prodrug thereof.

Acid stable liposomal compositions and methods for producing the same

Stable, non-toxic, calcium phosphate nanoparticles are formed that incorporate one or more oligonucleotides. RNAi nucleotides may be incorporated and, in particular, siRNA nucleotides. Since the siRNA nanoparticles dissociate leaving only naturally occurring residual materials, calcium and phosphate, along with the siRNA, they are particularly useful as carrier vehicles. The ability to incorporate more than one siRNA provides a means to block or knock down the translation of multiple targeted proteins at the same time.

Therapeutic calcium phosphate nanoparticle incorporating siRNA useful in treating disease

A system and method for optimizing the systemic delivery of growth-arresting lipid-derived bioactive drugs or gene therapy agents to an animal or human in need of such agents utilizing nanoscale assembly systems, such as liposomes, resorbable and non-aggregating nanoparticle dispersions, metal or semiconductor nanoparticles, or polymeric materials such as dendrimers or hydrogels, each of which exhibit improved lipid solubility, cell permeability, an increased circulation half life and pharmacokinetic profile with improved tumor or vascular targeting.

Method and system for systemic delivery of growth arresting, lipid-derived bioactive compounds

Non-aggregating resorbable calcium phosphosilicate nanoparticles (CPNPs) are bioconjugated to targeting molecules that are specific for particular cells. The CPNPs are stable particles at normal physiological pH. Chemotherapy and imaging agents may be integrally formed with the CPNPs so that they are compartmentalized within the CPNPs. In this manner, the agents are protected from interaction with the environment at normal physiological pH. However, once the CPNPs have been taken up, at intracellular pH, the CPNPs dissolve releasing the agent. Thus, chemotherapeutic or imaging agents are delivered to specific cells and permit the treatment and/or imaging of those cells. Use of the bioconjugated CPNPs both limits the amount of systemic exposure to the agent and delivers a higher concentration of the agent to the cell. The methods and principals of bioconjugating CPNPs are taught by examples of bioconjugation of targeting molecules for breast cancer, pancreatic cancer, and leukemia.

Bioconjugation of calcium phosphosilicate nanoparticles for selective targeting of cells in vivo

Gastrin mRNA down-regulation using either stable transfection of an antisense gastrin cDNA or one of three shRNA (short hairpin RNA) constructs achieves significant reduction in growth of human pancreatic cancer. Tumor growth rate and incidence of metastases in both wild type and transfected pancreatic cancer cells is directly proportional to the degrees of gastrin mRNA expression. In order to avoid rapid degradation of injected siRNA, nanoliposomes can be loaded with gastrin siRNA and used to deliver the siRNA to the tumors. Significant reduction of tumors in mice using siRNA loaded nanoliposomes is achieved. Uptake of pegylated nanoliposomes by tumor cells depends upon the pegylation percentage.

Composition and method for the treatment of gastrin mediated cancers

Nano-encapsulated photosensitizers and their use in the treatment of tumors and/or imaging is described. Preferably, the photosensitizers are encapsulated in a calcium phosphate nanoparticle (CPNP). Encapsulating the PS in a CPNP increases the half-life of the PS, increases absorption of the PS into the target cell tissue, increases the photostability of the PS, increases the photoefficiency of the PS, increases in vivo retention of the PS, or combinations thereof, ultimately making it a highly efficacious agent for use in photodynamic therapy, imaging target tissues, vessels, or tumors, and/or detecting or locating tumors.

In vivo photodynamic therapy of cancer via a near infrared agent encapsulated in calcium phosphate nanoparticles

Described herein are pharmaceutical compositions according to aspects of the present invention which include one or more hydrophilic antineoplastic chemotherapeutics, such as vinca alkyloid antineoplastic chemotherapeutics, encapsulated in ceramide anionic liposomes. Methods of treatment of a subject having cancer using the pharmaceutical compositions are described, along with methods of making ceramide anionic liposomes which encapsulate one or more hydrophilic antineoplastic chemotherapeutics in the aqueous interior of the ceramide anionic liposomes.

Ceramide anionic liposome compositions

The present invention provides a method for the synthesis of unagglomerated, highly dispersed, stable core/shell nanocomposite particles comprised of preparing a reverse micelle microemulsion that contains nanocomposite particles, treating the microemulsion with a silane coupling agent, breaking the microemulsion to form a suspension of the nanocomposite particles by adding an acid/alcohol solution to the microemulsion that maintains the suspension of nanocomposite particles at a pH of between about 6 and 7, and simultaneously washing and dispersing the suspension of nanocomposite particles, preferably with a size exclusion HPLC system modified to ensure unagglomeration of the nanocomposite particles. The primary particle size of the nanocomposite particles can range in diameter from between about 1 to 100 nm, preferably from between about 10 to 50 nm, more preferably about 10 to 20 nm, and most preferably about 20 nm.

Unagglomerated core/shell nanocomposite particles

A number of human disorders are characterized by degeneration or loss of specific cells, resulting in pathology associated with reduction or absence of cell function. Such diseases include neurodegenerative diseases and diabetes. Methods are described for obtaining a substantially homogeneous population of undifferentiated human embryonic stem cells including incubating a population of human embryonic stem cells with an amount of a selection agent. The selection agent is effective to reduce or eliminate differentiated embryonic stem cells from the population of cells such that a substantially homogeneous population of undifferentiated human embryonic stem cells is obtained. The substantially homogeneous population of undifferentiated embryonic stem cells may be produced without use of feeder cells.

Systems and methods for selection and maintenance of homogeneous and pluripotent human embryonic stem cells

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Harrisburg, PA, United States of America

Mark Kester