The present disclosure provides a nanocapsule comprising a hydrophilic core; and a hydrophobic shell enclosing the hydrophilic core. The hydrophobic shell contains an outer layer comprising fucoidan, a middle layer comprising carotenoids and metal oxide nanoparticles, and an inner layer comprising fucoidan and contacting the hydrophilic core. The present disclosure also provides use of the nanocapsule as disclosed herein in the manufacture of a medicament for treating and/or diagnosing diseases in a subject in need thereof.

Disclosed herein are methods of treatment for an intraocular pressure (IOP)-associated condition in a subject, that include administering to the subject an effective amount of a tissue plasminogen activator (tPA) therapeutic agent. In one embodiment, the IOP-associated condition is glaucoma. The administration of a tPA therapeutic agent can be an extended administration intended to cause a reduction in IOP in the subject for a period of at least one day to a year or more, relative to IOP levels in the subject prior to administration of the tPA therapeutic agent. The tPA therapeutic agent can be, for example, tPA, a tPA derivative, a small molecule direct or indirect tPA agonist, or a gene therapy vector.

A method of forming an implant in a tissue can include: providing an injectable liquid composition comprising one or more precursors of a crosslinkable composition; injecting the injectable composition into the tissue at the rate of about 10-12000 injections per minute and/or at an amount of 1.0E-02 ml to 1.0E-16 ml per injection; and crosslinking the one or more precursors of the crosslinkable composition so as to form a crosslinked composition.

The present invention pertains to an economic packed-bed perfusion system for the production of pharmaceutical grade of recombinant TNK-tPA. The present invention involves a cell culture process utilizing CHO cells more specifically in a micro/macro carriers based packed-bed perfusion system. The process of the present invention results in optimum cell growth and maintenance, and minimal build-up of toxic by-products such as lactate and ammonia. The system of the present invention discloses optimized process parameters to enable a resultant TNK-tPA with high yield and pharmaceutical grade purity. The process of the present invention is industrially applicable and possesses economy of scale.

Provided herein are particles comprising a polymer substrate comprising one or more hyaluronic acid chains; and two or more peptide moieties bound directly to each hyaluronic acid chain. In some embodiments, the two or more peptide moieties comprising collagen-binding peptide (CBP) and von Willebrand binding peptide (VBP). The particles can be utilized in, e.g., methods of hemostatic treatment.

The presently disclosed subject-matter provides specific compositions, conjugates, device, kits and systems for depleting fibrinolytic agents from biological fluids. The presently disclosed subject-matter further relates to the resulting biological fluid products that are devoid in fibrinolytic activity, therapeutic methods and uses thereof. The conjugates comprise a particle, at least one linker and at least one amino acid, derivative thereof or analog thereof being at least one of 4-(aminomethyl)-cyclo-hexane-carboxylic acid (tranexamic acid), epsilon-amino caproic acid, lysine, cyclohexanecarboxylic acid and 4-methyl-cyclohexanecarboxylic acid. A plurality of different conjugates (e.g. differing in particle size or type of linker) can be used.

A system for the physical manipulation of free magnetic rotors in a circulatory system using a remotely placed magnetic field-generating stator is provided. In one embodiment, the invention relates to the control of magnetic particles in a fluid medium using permanent magnet-based or electromagnetic field-generating stator sources. Such a system can be useful for increasing the diffusion of therapeutic agents in a fluid medium, such as a human circulatory system, which can result in substantial clearance of fluid obstructions, such as vascular occlusions, in a circulatory system resulting in increased blood flow. Examples of vascular occlusions targeted by the system include, but are not limited to, atherosclerotic plaques, including fibrous caps, fatty buildup, coronary occlusions, arterial stenosis, restenosis, vein thrombi, arterial thrombi, cerebral thrombi, embolisms, hemorrhages, other blood clots, and very small vessels.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders. The present disclosure relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A.sup.386 (Cholix.sup.386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. The systems and methods described herein provide for: the ability to deliver macromolecule doses without injections; the ability to deliver cargo such as siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders.