Abstract: The present invention provides microfluidic systems and methods for the production of particles (e.g., nanoparticles) for drug delivery. The present invention provides microfluidic devices useful for production of particles by nanoprecipitation. The present invention provides highly homogenous compositions of particles produced by inventive microfluidic devices.

Abstract: Screening of a library of particles in vivo and/or in vitro using Polyplex Iterative Combinatorial Optimization (PICO) allows for the design of particles for targeting a specific organ, tissue (e.g., cancer), or cell. Particles may, for example, include different targeting agents (e.g., aptamers or plurality of aptamers) on their surfaces, and the aptamer or aptamers may be evolved to provide better targeting of the particles. Libraries of particles are enriched in characteristics of particles that have been found to migrate to a tissue of interest, be taken up by cells, etc. The process may be repeated to engineer particles of a desired specificity or biological function.

Abstract: The present invention generally relates to nanoparticles with an amphiphilic component. One aspect of the invention is directed to a method of developing nanoparticles with desired properties. In one set of embodiments, the 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. In some cases, the nanoparticle may contain a drug. Other aspects of the invention are directed to methods using nanoparticle libraries.

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: 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. The nanocarriers are capable of targeting antigen presenting cells when administered to a subject. 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: Screening of a library of particles in vivo and/or in vitro using Polyplex Iterative Combinatorial Optimization (PICO) allows for the design of particles for targeting a specific organ, tissue (e.g., cancer), or cell. Particles may, for example, include different targeting agents (e.g., aptamers or plurality of aptamers) on their surfaces, and the aptamer or aptamers may be evolved to provide better targeting of the particles. Libraries of particles are enriched in characteristics of particles that have been found to migrate to a tissue of interest, be taken up by cells, etc. The process may be repeated to engineer particles of a desired specificity or biological function.

Abstract: Sub-100 micron multimodal nanoparticles have four main components: 1) a target element (peptides, lipids, antibodies, small molecules, etc.) that can selectively bind to cells, tissues, or organs of the body; 2) a diagnostic agent such as a fluorophore or NMR contrast agent that allows visualization of nanoparticles at the site of delivery and/or a therapeutic or prophylactic agent; 3) an outside “stealth” layer that allows the particles to evade recognition by immune system components and increase particle circulation half-life; and 4) a biodegradable polymeric material, forming an inner core which can carry therapeutics and release the payloads at a sustained rate after systemic, intraperitoneal, or mucosal administration. These particles possess excellent stability, high loading efficiency, multiple agent encapsulation, targeting and imaging. They are targeted to sites of, or associated with, inflammation caused by a disease, disorder; trauma, chemotherapy or radiation.

Abstract: Provided herein are new compositions including an inactivated pathogen and one or more adjuvant-loaded polymeric nanoparticles, wherein the adjuvant-loaded nanoparticles are bound to the inactivated pathogen. These compositions are useful for preventing and/or treating diseases caused by the specific pathogens, especially when administered to a subject's mucosal membranes.

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 an 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: Water-responsive composite materials are provided containing a polymeric matrix and a water-responsive gel integrated into the polymeric matrix. The water-responsive gel can include a polyol or an alkoxylated polyol crosslinked by reversibly hydrolysable bonds, such as borate ester bonds. The polymeric matrix can include conjugated polymers such as poly(pyrrole) containing polymers. The composite material is capable of rapid actuation in the presence of a water gradient and can exhibit power densities greater than 1 W/kg. Methods of making water-responsive composite materials are provided, including by electropolymerization. Devices containing water-responsive composite materials are provided for sensing, locomotion, and power generation.

Abstract: Provided herein are compositions that contain a nanoparticle containing a plurality of polymers, wherein at least a fraction of the polymers comprise a hydrophobic polymer, a topoisomerase inhibitor, and a Pt-containing chemotherapeutic agent, where the polymers self-assemble in an aqueous liquid to form the nanoparticle, and where the Pt-containing chemotherapeutic agent and the topoisomerase inhibitor are present within the hydrophobic core of the nanoparticle in a ratio of between about 24:1 to about 1:24. Also provided are methods of reducing the proliferation of a cancer cell and methods of treating cancer in a subject that include the use of these compositions. Also provided are methods of making these nanoparticles.

Abstract: An apparatus provides targeted placement of openings for infusing fluids into a body. 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 due to contraction of an element made of interlaced flexible elements. A multi-opening needle is provided in some embodiments wherein placement of one of the openings in a target region with a relatively lower external pressure allows pressurized fluid to exit the needle while openings remaining in higher pressure, non-target regions do not release substantial amounts of the fluid.

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: 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 a 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: 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: 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: 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: The present invention provides a drug delivery system for targeted delivery of therapeutic agent-containing particles to tissues, cells, and intracellular compartments. The invention provides targeted particles comprising a particle, one or more targeting moieties, and one or more therapeutic agents to be delivered and pharmaceutical compositions comprising inventive targeted particles. The present invention provides methods of designing, manufacturing, and using inventive targeted particles and pharmaceutical compositions 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 having a plurality of nicotine moieties. The invention provides pharmaceutical compositions comprising nanocarriers. The present invention provides methods of designing, manufacturing, and using nanocarriers and pharmaceutical compositions thereof. For example, the present invention describes nanocarriers capable of eliciting an immune response and the production of anti-nicotine antibodies.

Abstract: An apparatus provides feedback regarding the material in which tip of the apparatus is located as the tip is advance 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.