The present invention encompasses prodrug compositions, nanoparticles comprising one or more prodrugs, and methods of use thereof.

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii):

##STR00001##

wherein R.sup.3 and R.sup.4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.5-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18 alkenyl, branched C.sub.3-C.sub.18 alkenyl, aryl, aryl-C.sub.1-C.sub.18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

The present invention provides a polyion complex which can efficiently deliver mRNA into a living body as well as a therapeutic agent and a therapeutic method of arthropathy in which the polyion complex is used. For example, there is provided a polyion complex comprising a cationic polymer and mRNA, wherein the cationic polymer is a polymer comprising a cationic unnatural amino acid as a monomer unit and the cationic unnatural amino acid is an amino acid having a group represented by —(NH—(CH.sub.2).sub.2).sub.p—NH.sub.2, wherein p is 2, 3 or 4, as a side chain.

In the present invention, the development of various oil-in-water (O/W) nanoemulsions containing an oil phase or oil core, preferably selected from vitamin E or oleic acid, stabilized by a sphingolipid of the sphingomyelin type, and optionally other lipids such as phospholipids, cholesterol, octadecylamine, DOTAP (N-[1-(2,3-Dioleoyloxy) propyl]-N, N, N-trimethylammonium methyl-sulfate), and PEGylated derivatives (derivatives with polyethylene glycol), for use as a nanotech vehicle, in particular for the management of cancer and metastatic disease, is herein described. Said nanoemulsions can be functionalized with ligands capable of interacting or binding to receptors expressed on the cell membrane of tumor cells, and in particular capable of interacting or binding to receptors expressed on the membrane of primary and/or disseminated or metastatic tumor cells. Also, antitumor drugs or therapeutic biomolecules can be encapsulated in said nanoemulsions and, finally, contrast agents can be incorporated for their use in the in vivo diagnosis in said nanoemulsions.

In the present invention, the use of the TAS1R3 receptor as a biomarker for application in cancer diagnosis, monitoring, and therapy is described for the first time. In this sense, the authors of the present invention have demonstrated that TAS1R3 is a biomarker of interest in oncology, useful for the diagnosis of the disease, and capable of providing relevant information thereupon, to monitor the evolution, select the treatment, and selectively direct therapeutic molecules. It has been determined that it is possible to identify therapies against this receptor, and that it is also possible to direct conjugates and controlled release systems of drugs, such as nanoparticles, observing a very effective intracellular accumulation thereof in primary, disseminated and metastatic tumor cells. On the other hand, the presence of TAS1R3 in circulating tumor cells (CTCs) has also been demonstrated. These are tumor cells released into the bloodstream by the primary tumor and are considered key factors in the creation of metastases, so that their detection in early stages will serve as an early detector of metastasis, and are also useful in monitoring the disease and evaluating of the response to drugs.

The present invention relates to complex particles using methylene blue for treating a skin disease caused by Propionibacterium acnes or Staphylococcus aureus and a composition for treatment including the complex particles. The complex particles in the present invention can be used as a photosensitizer for a photodynamic therapy and complex particles having a micelle form in which hydrophilic methylene blue and two hydrophobic organic acids are combined, and as a result, pore penetration is easy and an occlusion time can be significantly reduced to 30 minutes as compared with conventional phototherapy requiring an occlusion time of 1 hour to 3 hours. Further, in order to reduce side effects of a residual photosensitizer in phototherapy using an existing photosensitizer due to photoreaction and photobleaching of the methylene blue-organic acid complex, a light protection (light blocking or light shielding) time when contact of light needs to be avoided for 24 hours or more after treatment can be significantly reduced to 3 hours, and target treatment for Propionibacterium acnes, Staphylococcus aureus, or the like which is a cause of acne is possible.

The present disclosure provides method of making a nanoparticle complex wherein the nanoparticle complex comprises a ligand and a metal cation. The disclosure also provides nanoparticle complexes, methods of treating a disease in a patient utilizing the nanoparticle complexes, methods of identifying a disease in a patient utilizing the nanoparticle complexes, and kits involving the nanoparticle complexes.

The subject invention pertains to polyacrylate homopolymers produced from acrylolated drug monomers. The homopolymers can be produced in the form of nanoparticles. The nanoparticles comprising the homopolymers can be produced via a free radical-induced emulsion polymerization of the acrylolated drug monomers to produce an aqueous emulsion of uniformly sized nanoparticles. The homopolymers of the invention containing acrylolated antibiotic monomers can be active against Gram-positive and Gram-negative bacteria, such as Staphylococcus aureus and Escherichia coil. Accordingly, methods are provided of treating a disease, for example, an infection, by administering to a subject the homopolymers, homopolymeric nanoparticles, or emulsions containing homopolymeric nanoparticles of the invention.

Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises ##STR00001##
wherein R′ is —H or —CH.sub.3, wherein R is —NR.sup.1R.sup.2, wherein R.sup.1 and R.sup.2 are alkyl groups, wherein R.sup.1 and R.sup.2 are the same or different, wherein R.sup.1 and R.sup.2 together have from 5 to 16 carbons, wherein R.sup.1 and R.sup.2 may optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.