Abstract: An apparatus provides feedback regarding the material in which tip of the apparatus is located as the tip is advanced into matter of varying resistances. The apparatus responds to a change in pressure, force, or other parameter such that when the tip reaches matter of a certain resistance, a change in the parameter is sensed. The apparatus provides a driving force to a penetrating medical device, such as a needle, when the apparatus tip encounters material of high resistance. When the apparatus tip encounters a low resistance material, no further driving force is applied to the apparatus. An inner core may be advanced into the low resistance material for deployment of a gas or a liquid as desired.

Abstract: Receptor-targeted nanoparticles (R-NPs) are provided for selective transport into and through targeted tissues of therapeutic, prophylactic and diagnostic agents. R-NPs can include polymeric particle, lipid particles, inorganic particles, or a combination thereof with a targeting moiety selective for binding to a receptor on the cells where the agent is to be delivered, where the receptor mediates transcytosis of the nanoparticle into and through the cells. In a preferred embodiment, the targeting moiety is the neonatal Fc receptor. Examples demonstrate Fc-targeted nanoparticles which are actively transported across the intestinal epithelium, providing a route for the oral delivery of nanoparticle encapsulated active agents including peptides such as insulin.

Abstract: Bone- and metal-targeted polymeric nanoparticles are provided. Exemplary nanoparticles have three main components: 1) a targeting element that can selectively bind to bone, minerals, or metal ions; 2) a layer of stealth to allow the polymer to evade immune response; and 3) a biodegradable polymeric material, forming an inner core which can carry therapeutics or other diagnostics. Preferred nanoparticles contain a blend of target-element polymer conjugate and polymer that optimizes the ligand density on the surface of the nanoparticle to provide improved targeting of the nanoparticle. The ratio of target-element polymer conjugate to polymer can also be optimized to improve the half-life of the nanoparticles in the blood of the subject. The nanoparticles also exhibit prolonged, sustained release of therapeutic agents loaded into the particles.

Abstract: Provided herein are disulfide polymers, methods of their preparation, compositions, and methods of using the same. For example, provided herein are polymers having at least one repeating unit according to Formula (I):or Formula (II): and nanoparticles and compositions including the same. The polymers and compositions provided herein may be used, for example, in the encapsulation of drugs for a slow release drug administration in the treatment or imaging of diseases.

Abstract: Methods for making particles, such as nanoparticles, devices useful in the methods, and particles made by the method are described herein. The methods involves the use of microfluidic device, such that upon mixing solutions of the materials to form the particles (or a solution of the material or materials to form the particles and a non-solvent for the material or materials) at least two symmetrical microvortices are formed simultaneously. The method can be used to prepare polymeric or non-polymeric particles and hybrid particles, such as lipid-polymer hybrid particles, as well as such particles containing one or more agents associated with the particles.

Abstract: This invention relates to amphiphile-polymer particles comprising obtaining a first solution comprising a water-insoluble polymer, a payload and a first amphiphile in a water-miscible solvent; mixing the first solution with an aqueous second solution to form an aqueous composition comprising a particle comprising a water-insoluble polymeric core comprising the water-insoluble polymer; the payload; and the first amphiphile.

Abstract: This disclosure relates to nanoparticles, compositions, methods of making, and methods of use thereof.

Abstract: A method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. The nanoparticle may contain a drug. The moiety may include a polypeptide or a polynucleotide, such as an aptamer. The moiety may be a targeting moiety, an imaging moiety, a chelating moiety, a charged moiety, or a therapeutic moiety. Another aspect is directed to systems and methods of producing such polymeric conjugates. In some embodiments, a solution containing a polymer is contacted with a liquid, such as an immiscible liquid, to form nanoparticles containing the polymeric conjugate. Other methods use such libraries, use or administer such polymeric conjugates, or promote the use of such polymeric conjugates. Kits involving such polymeric conjugates are also described.

Abstract: This disclosure relates to particles (e.g., nanoparticles and microparticles) that display multiple functionalized surface domains in a controlled mosaic pattern. The disclosure also provides simple methods to create various particles that have multiple functionalized surface domains while allowing the use of a wide variety of diverse core structures. The multiple functionalized domains provide controllable particle binding and orientation, and controlled and sustained drug release profiles.

Abstract: A composition for delivering an active agent to a patient. The composition includes a polymer core encapsulating the active agent and a mucoadhesive coating disposed about the core. The polymer may include covalently linked poly(ethylene glycol) chains, and the mucoadhesive coating may be selected to facilitate transfer of the particle through the intestinal mucosa. A molecular weight and cross-link density of the polymer may be selected such that the polymer core will decompose in a predetermined time interval. The fraction of the dose of the drug entering the system at circulation during the predetermined time interval may be between about 0.25% and about 25%. The composition may be formulated as a plurality of nanoparticles or microparticles that are combined with a pharmaceutically acceptable carrier to produce an edible or inhalable drug product.

Abstract: Nanoparticles having a positive feedback delivery system include an agent specific for a target in combination with a target inducing agent. Upon administration to a subject, the targeting moiety on the nanoparticles binds to available targets in the subject. The nanoparticles release the target inducing agent and, optionally, a therapeutic agent, at the site where the nanoparticles bind the target. The inducing agent causes additional targets to be expressed. More nanoparticles bind to the additional, induced targets. By inducing additional targets to be expressed at specific regions in the subject that require treatment, more nanoparticles can bind to the targets in that specific region of interest, increasing the concentration of nanoparticles at a specific area of subject is increased.

Abstract: A particle includes an aqueous core; a first amphiphilic layer surrounding the aqueous core; and a polymeric matrix surrounding the first amphiphilic layer.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Abstract: Self-assembled gel compositions including a gelator, e.g., an enzyme-cleavable gelator, e.g., having a molecular weight of 2500 or less, are described. The self-assembled gel compositions can encapsulate one or more agents. Methods of making the self-assembled gel compositions, and methods of drug delivery using the self-assembled gel compositions are also described.

Abstract: Receptor-targeted nanoparticles (R-NPs) are provided for selective transport into and through targeted tissues of therapeutic, prophylactic and diagnostic agents. R-NPs can include polymeric particle, lipid particles, inorganic particles, or a combination thereof with a targeting moiety selective for binding to a receptor on the cells where the agent is to be delivered, where the receptor mediates transcytosis of the nanoparticle into and through the cells. In a preferred embodiment, the targeting moiety is the neonatal Fc receptor. Examples demonstrate Fc-targeted nanoparticles which are actively transported across the intestinal epithelium, providing a route for the oral delivery of nanoparticle encapsulated active agents including peptides such as insulin.

Abstract: The present invention generally relates to polymers and particles, such as nanoparticles. The particles and polymers generally include one or more buffering components. Additionally, the particles and polymers may include two or more components that impart useful properties (functionalities). The particles and polymers, for example, may include a buffering component and a degradable component. As described herein, the particles and polymers may also include a hydrophilic component and/or a cleavable bond component. The particles and polymers described herein have been found to be particularly effective when used for delivery of one or more agents, such as one or more pharmaceutical agents. Other aspects of the invention are directed to methods of using or administering such particles or polymers, kits involving such particles or polymers, and the like.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface and an immunostimulatory moiety. In some embodiments, the immunostimulatory moiety is adjuvant. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Abstract: This disclosure relates to particles (e.g., nanoparticles and microparticles) that display multiple functionalized surface domains in a controlled mosaic pattern. The disclosure also provides simple methods to create various particles that have multiple functionalized surface domains while allowing the use of a wide variety of diverse core structures. The multiple functionalized domains provide controllable particle binding and orientation, and controlled and sustained drug release profiles.