The present system is directed in several embodiments to a method of administration of a therapeutic composition for protection of the brain of a subject at risk of injury leading to traumatic brain injury (TBI) and/or treatment of injury to the brain resulting from TBI. The method includes administering one or more therapeutic compositions comprising an effective amount of insulin directly to the subject patient's CNS, with no to minimal systemic exposure. Preferably, this method comprises administration of an effective amount of insulin to the upper third of a patient's nasal cavity, thereby bypassing the patient's blood-brain barrier and delivering the therapeutic composition directly to the patient's central nervous system.

The disclosure provides methods of preventing or treating Type 1 diabetes in a mammalian subject, reducing risk factors associated with Type 1 diabetes, and/or reducing the likelihood or severity of Type 1 diabetes. A method of attenuating an antigenic response in a mammal to at least one Type 1 diabetes related-antigen is also provided. The methods include sublingually administering an effective amount of an insulin-related peptide to a subject.

The disclosure provides methods of preventing or treating Type 1 diabetes in a mammalian subject, reducing risk factors associated with Type 1 diabetes, and/or reducing the likelihood or severity of Type 1 diabetes. A method of attenuating an antigenic response in a mammal to at least one Type 1 diabetes related-antigen is also provided. The methods include sublingually administering an effective amount of an insulin-related peptide to a subject.

A method for improving the solubility of a physiologically active protein or peptide compared to that of a physiologically active protein or peptide which is not conjugated to an immunoglobulin Fc fragment is disclosed. The method includes steps of conjugating the physiologically active protein or peptide to an immunoglobulin Fc fragment. Also disclosed is a composition for improving the solubility of a physiologically active protein or peptide, which contains an immunoglobulin Fc fragment. The composition improves the solubility compared to a composition without an immunoglobulin Fc fragment.

A method for improving the solubility of a physiologically active protein or peptide compared to that of a physiologically active protein or peptide which is not conjugated to an immunoglobulin Fc fragment is disclosed. The method includes steps of conjugating the physiologically active protein or peptide to an immunoglobulin Fc fragment. Also disclosed is a composition for improving the solubility of a physiologically active protein or peptide, which contains an immunoglobulin Fc fragment. The composition improves the solubility compared to a composition without an immunoglobulin Fc fragment.

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. 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. In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent.

Products, systems and methods are disclosed for lowering the concentrations of at least one of preservatives and fibrils in a liquid insulin composition. One method comprises replacing at least a portion of at least one of phenol and m-cresol with at least one of cyclodextrins, cyclodextrin polymers, cyclodextrin beads, and an ion exchange resin.

Products, systems and methods are disclosed for lowering the concentrations of at least one of preservatives and fibrils in a liquid insulin composition. One method comprises replacing at least a portion of at least one of phenol and m-cresol with at least one of cyclodextrins, cyclodextrin polymers, cyclodextrin beads, and an ion exchange resin.

Disclosed herein are compositions and in vitro and in vivo methods for reprogramming post-natal (adult and juvenile) tissue into insulinogenic cells. These compositions and methods are useful for a variety of purposes, including the development of diabetes therapies.

Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic islet cells. In some aspects, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.