Nanoparticles include a core and one or more targeting moieties, as well as one or more contrast agents or one or more therapeutic agents. The contrast agents or therapeutic agents may be contained or embedded within the core. If the nanoparticle includes therapeutic agents, the agents are preferably released from the core at a desired rate. The core may be biodegradable and may release the agents as the core is degraded or eroded. The targeting moieties preferably extend outwardly from the core so that they are available for interaction with cellular components, which interactions will target the nanoparticles to the appropriate cells, such as apoptotic cells; organelles, such as mitochondria; or the like. The targeting moieties may be tethered to the core or components that interact with the core.

The present invention relates to a poly (ester amide) (PEA) having a chemical formula described by structural formula (IV), ##STR00001##
wherein m+p varies from 0.9-0.1 and q varies from 0.1 to 0.9 m+p+q=1 whereby m or p could be 0 n is about 5 to about 300; (pref. 50-200) R.sub.1 is independently selected from the group consisting of (C.sub.2-C.sub.20 alkylene, (C.sub.2-C.sub.20) alkenylene, (R.sub.9COOR.sub.10OCOR.sub.9), CHR.sub.11OCOR.sub.12COOCR.sub.11 and combinations thereof; R.sub.3 and R.sub.4 in a single backbone unit m or p, respectively, are independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, (C.sub.6-C.sub.10)aryl, (C.sub.1-C.sub.6)alkyl, (CH.sub.2)SH, (CH.sub.2)S(CH.sub.3), CH.sub.2OH, CH(OH)CH.sub.3, (CH.sub.2).sub.4NH.sub.3+, (CH.sub.2).sub.3NHC(NH.sub.2+)NH.sub.2, CH.sub.2COOH, (CH.sub.2)COOH, CH.sub.2CONH.sub.2, CH.sub.2CH.sub.2CONH.sub.2, -- CH.sub.2CH.sub.2COOH, CH.sub.3CH.sub.2CH(CH.sub.3), (CH.sub.3).sub.2CHCH.sub.2, H.sub.2N(CH.sub.2).sub.4, Ph-CH.sub.2, CHCCH.sub.2, HO-p-Ph-CH.sub.2, (CH.sub.3).sub.2CH, Ph-NH, NH(CH.sub.2).sub.3C, NHCHNCHCCH.sub.2. R.sub.5 is selected from the group consisting of (C.sub.2-C.sub.20)alkylene, (C.sub.2-C.sub.20)alkenylene, alkyloxy or oligoethyleneglycol R.sub.6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III); ##STR00002## R.sub.7 is selected from the group consisting of (C.sub.6-C.sub.10)aryl (C.sub.1-C.sub.6)alkyl R.sub.8 is (CH2)4-; R.sub.9 or R.sub.10 are independently selected from C.sub.2-C.sub.12 alkylene or C.sub.2-C.sub.12 alkenylene. R.sub.11 or R.sub.12 are independently selected from H, methyl, C.sub.2-C.sub.12 alkylene or C.sub.2-C.sub.12 alkenylene whereby a is at least 0.05 and b is at least 0.05 and a+b=1.

Disclosed are synthetic nanocarrier compositions with coupled adjuvant compositions as well as related methods.

Compositions and methods for treating eye disorders by administering a drug delivery system into an eye compartment of the patient, wherein the drug delivery system contains a particle containing a core; a coating associated with the particle, wherein the coating is covalently or non-covalently associated with the particle and presents a hydrophilic region to the environment around the particle; and a therapeutic agent are disclosed. The eye compartment can exhibit reduced inflammation or TOP after administration of the drug delivery systems to a patient than if a drug delivery system including an uncoated particle were administered to the patient.

A composition includes an isolated cell; at least one particle within said cell; and at least one active agent associated with the particle, wherein the active agent is capable of being released from the cell. A method includes administration of such a cell to a subject.

The present invention provides methods of delivering a composition comprising nanoparticles that comprise a macrolide and an albumin by directly injecting the nanoparticle composition into the blood vessel wall or the tissue surrounding the blood vessel wall. The methods can be used for inhibiting negative remodeling or vascular fibrosis in the blood vessel and are useful for treating various diseases.

The present invention provides compositions and methods useful for delivering agents to target cells or tissues, for example nerve cells and other cells in the central nervous system. The compositions and methods are useful for delivering agents across the blood-brain barrier. The present invention also provides methods of using the compositions provided by the present invention to deliver agents, for example therapeutic agents for the treatment of neurologically related disorders.

The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (T.sub.reg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound T.sub.reg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

The present invention relates to a vitamin B6-coupled poly(ester amine) (VBPEA) as a gene carrier and a method for preparing the gene carrier. Moreover, the present invention relates to a gene delivery complex comprising a therapeutic gene coupled to the gene carrier and a pharmaceutical formulation for gene therapy, which comprises the gene delivery complex as an active ingredient. In addition, the present invention relates to gene therapy utilizing the gene carrier, the gene delivery complex or the pharmaceutical formulation. The VBPEA of the invention has a significantly high gene delivery rate compared to existing gene carriers and a complex of the VBPEA with DNA has little or no cytotoxicity and shows a very high in vivo transfection efficiency. In addition, a complex of the VBPEA with siRNA shows high gene silencing efficiency and can induce a high rate of cell death and the inhibition of cell proliferation in cancer cells, suggesting that it can be used for anticancer gene therapy. Thus, the gene carrier VBPEA of the invention can be used as an experimental gene carrier and can also be widely used in gene therapy against various diseases depending on the kind of therapeutic gene.

The present disclosure relates to microparticles or nanoparticles comprising a polyesteramide (PEA) having a chemical formula described by structural formula (IV), ##STR00001##
wherein m+p varies from 0.9-0.1 and q varies from 0.1 to 0.9; m+p+q=1 whereby m or p could be 0; n is about 5 to about 300; (pref. 50-200); R.sub.1 is independently selected from the group consisting of (C.sub.2-C.sub.20) alkylene, (C.sub.2-C.sub.20) alkenylene, (R.sub.9COOR.sub.10OCOR.sub.9), CHR.sub.11OCOR.sub.12COOCR.sub.11 and combinations thereof; R.sub.3 and R.sub.4 in a single backbone unit m or p, respectively, are independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, (C.sub.6-C.sub.10)aryl, (C.sub.1-C.sub.6)alkyl, (CH.sub.2)SH, (CH.sub.2).sub.2S(CH.sub.3), CH.sub.2OH, CH(OH)CH.sub.3, (CH.sub.2).sub.4NH.sub.3+, (CH.sub.2).sub.3NHC(NH.sub.2+)NH.sub.2, CH.sub.2COOH, (CH.sub.2)COOH, CH.sub.2CONH.sub.2, CH.sub.2CH.sub.2CONH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.3CH.sub.2CH(CH.sub.3), (CH.sub.3).sub.2CHCH.sub.2, H.sub.2N(CH.sub.2).sub.4, Ph-CH.sub.2, CHCCH.sub.2, HO-p-Ph-CH.sub.2, (CH.sub.3).sub.2CH, Ph-NH, NH(CH.sub.2).sub.3C, NHCHNCHCCH.sub.2; R.sub.5 is selected from the group consisting of (C.sub.2-C.sub.20)alkylene, (C.sub.2-C.sub.20)alkenylene, alkyloxy or oligoethyleneglycol; R.sub.6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III); R.sub.7 is (C.sub.6-C.sub.10)aryl (C.sub.1-C.sub.6)alkyl; R.sub.8 is (CH.sub.2).sub.4; R.sub.9 or R.sub.10 are independently selected from C.sub.2-C.sub.12 alkylene or C.sub.2-C.sub.12 alkenylene; and R.sub.11 or R.sub.12 are independently selected from H, methyl, C.sub.2-C.sub.12 alkylene or C.sub.2-C.sub.12 alkenylene; whereby a is at least 0.05 and b is at least 0.05 and a+b=1.