Abstract: The modification of biomolecules, small molecules, and other agents of via conjugation of excipients, tags, or labels is of great importance. For example, the modification of therapeutic agents can confer improved stability, solubility, duration of action, or pharmacological properties. Supramolecular chemistry utilizes specific, directional, reversible, non-covalent molecular recognition motifs in order to achieve organization of molecules, and can be used to complex tags to agents of interest (e.g., insulin, glucagon, antibodies). The present invention provides useful supramolecular complexes wherein an agent of interest is specifically bound to a host via non-covalent interactions, and wherein the host is conjugated to a tag. The present invention also provides methods and compounds useful in preparing supramolecular complexes, and methods of treating diseases using the supramolecular complexes.

Abstract: Network materials which exhibit both shear thinning and self-healing properties are disclosed. The networks contain particles and gel-forming compounds. The networks are useful for a variety of biomedical uses, including drug delivery.

Abstract: Apparatus, kits, and methods for administering a substance are presented. A device for administering a substance includes an elongated body having a proximal end and a distal end, the elongated body defining an internal chamber extending between the proximal end and the distal end to direct the substance to the distal end, the distal end to connect with a tip, the tip to be at least partially inserted into an orifice of a body lumen of a subject, the tip having a shape configured to reduce leakage of the substance from the orifice upon the at least partial insertion. The tip includes an opening to pass the substance from the internal chamber into the body lumen; and a transducer to emit an ultrasound wave from the tip into the body lumen, thereby administering the substance to tissue in the body lumen.

Abstract: Articles for rapid release of components including, for example, quick release capsules, are generally provided. Advantageously, in some embodiments, the articles described herein may be configured to prevent fluid from contacting a component h contained therein (e.g., tissue interfacing component) or payload contained therein until a desired time, e.g., the time at which the component is configured to release from the article to a location internal to a subject (e.g., localize to a tissue wall in the subject). In some embodiments, the article comprises a first compartment and a second compartment not in fluid communication with the first compartment. In some embodiments, the first compartment and second compartment are fluidically isolated. For example, in some cases, the first compartment comprises a mechanism for releasing a component contained within the article and the second compartment comprises the component.

Abstract: Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject).

Abstract: Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the residence articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the residence article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the residence article may be configured to control drug release e.g., with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the residence articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the residence article includes dimensions configured for transesophageal retrieval. In some cases, the residence articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

Abstract: Microparticulate compositions and methods for delivery and pulsatile release of one or more sting agonists and/or receptors have been developed. The compositions include polymeric microdevices formed from biodegradable and biocompatible polymers or co-polymers thereof including a shell and compartment(s) or discrete regions in the compartment(s) formed by an additive process such as micromolding, three dimensional printing and lithography. The compositions include microdevices that release individual doses of incorporated STING agonist and/or receptors at defined times, for example, in pulses up to several months after administration with essentially no leakage between releases.

Abstract: Surface-modified cell containing a cell and a conformal coating on the extracellular surface of the cell are described. The conformal coating contains two or more layers containing particles (e.g. nanoparticles) or macromolecules. The cell is an islet cell, a B cell, or a T cell. The macromolecules or particles are formed from zwitterionic polymers. Covalent linkages are employed to link the particles or macromolecules to a cell surface molecule containing an abiotic functional group, or between macromolecules and/or particles in adjacent layers. Also described are methods of making and using a surface-modified cell.

Abstract: Drug-eluting devices and methods for the treatment of tumors of the pancreas, biliary system, gallbladder, liver, small bowel, or colon, are provided. Methods include deploying a drug-eluting device having a film which includes a mixture of a degradable polymer and a chemotherapeutic drug, wherein the film has a thickness from about 2 ?m to about 1000 ?m, into a tissue site and releasing a therapeutically effective amount of the chemotherapeutic drug from the film to treat the tumor, wherein the release of the therapeutically effective amount of the drug from the film is controlled by in vivo degradation of the polymer at the tissue site.

Abstract: Compositions and methods for modified dendrimer nanoparticle (“MDNP”) delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules to the cells of a subject have been developed. MDNPs efficiently drive proliferation of antigen-specific T cells against intracellular antigen, and potentiate antigen-specific antibody responses. MDNPs can be multiplexed to deliver two or more different repRNAs to modify expression kinetics of encoded antigens and to simultaneous deliver repRNAs and mRNAs including the same UTR elements that promote expression of encoded antigens.

Abstract: Provided herein are pharmaceutical compositions for local administration of metabolic inhibitors, methods of locally administering such compositions, and rapid diagnostic methods for identifying mutant allele during the course of a surgical procedure.

Abstract: Microdevices with complex three-dimensional (3D) internal and external structures are described. The microdevices are made by a method combining micromolding and soft lithography with an aligned sintering process. The microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), generates microdevices with complex geometries and with fully-enclosed internal cavities containing a solid or liquid. The microdevices are useful for biomedical, electromechanical, energy and environmental applications.

Abstract: Gene editing can be performed by introducing gene-editing components into a cell by mechanical cell disruption. Related apparatus, systems, techniques, and articles are also described. The methods and systems of the invention solve the problem of intracellular delivery of gene editing components and gene editing complexes to target cells. The results described herein indicate that delivery of gene editing components, e.g., protein, ribonucleic acid (RNA), and deoxyribonucleic acid (DNA), by mechanical disruption of cell membranes leads to successful gene editing. Because intracellular delivery of gene editing materials is a current challenge, the methods provide a robust mechanism to engineer target cells without the use of potentially harmful viral vectors or electric fields.

Abstract: A method and device for preferentially delivering a compound such as an antigen to the cytosol of an immune cell. The method comprises passing a cell suspension comprising the target immune cell through a microfluidic device and contacting the suspension with the compound(s) or payload to be delivered.

Abstract: 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): wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

Abstract: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.

Abstract: Enteric elastomers and related methods are generally provided. In some embodiments, the enteric elastomer is a polymer composite. Certain embodiments comprise a polymer composite in which hydrogen bonds within two carboxyl group-containing polymers cross-link the polymer networks into an elastic and pH-responsive polymer composite. Advantageously, this polymer composite has the capacity of being stable and elastic in an acidic environment such as that of the stomach but can be dissolved in a neutral pH environment such as that of the small and large intestines. In some embodiments, the polymer composites described herein comprise a mixture of two or more polymers with carboxyl functionality such that the two or more polymers form hydrogen bonds. In certain embodiments, the polymer composite has both enteric and elastic properties.

Abstract: Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.

Abstract: Methods and compositions for determining multiplex interactions between drugs and drug transporters using an intestinal tissue explant are provided.

Abstract: Among other things, the present disclosure provides compositions and methods for an elastomeric cross-linked polyester material. Such an elastomeric cross-linked polyester material, in some embodiments, comprises a plurality of polymeric units of the general formula (-A-B-)p, wherein p is an integer greater than 1; and a plurality of urethane cross-links each of which covalently links two polymeric units to one another, which two linked polymeric unit each had at least one free hydroxyl or amino group prior to formation of the crosslink.