Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity.

Nucleic acid-binding polymers can have anti-inflammatory properties and beneficial effects in animal models of infection, trauma, cancer, and autoimmunity. PAMAM G3, a polyamidoamine dendrimer, is fully cationic bearing 32 protonable surface amines. However, while PAMAM G3 treatment leads to improved outcomes for mice infected with influenza, at risk of cancer metastasis, or genetically prone to lupus, its administration can lead to serosal inflammation and elevation of biomarkers of liver and kidney damage. Variants with reduced density of cationic charge through the interspersal of hydroxyl groups were evaluated as potentially better-tolerated alternatives. Notably, the variant PAMAM G3 50:50, similar in size as PAMAM G3 but with half the charge, was not toxic in cell culture, less associated with weight loss or serosal inflammation after parenteral administration, and remained effective in reducing glomerulonephritis in lupus-prone mice. Identification of such modified scavengers should facilitate their development as safe and effective anti-inflammatory agents.

Elastin-Like Polypeptides for Biomedical Applications.

Elastin-like polypeptides (ELPs) are stimulus-responsive biopolymers derived from human elastin. Their unique properties-including lower critical solution temperature phase behavior and minimal immunogenicity-make them attractive materials for a variety of biomedical applications. ELPs also benefit from recombinant synthesis and genetically encoded design; these enable control over the molecular weight and precise incorporation of peptides and pharmacological agents into the sequence. Because their size and sequence are defined, ELPs benefit from exquisite control over their structure and function, qualities that cannot be matched by synthetic polymers. As such, ELPs have been engineered to assemble into unique architectures and display bioactive agents for a variety of applications. This review discusses the design and representative biomedical applications of ELPs, focusing primarily on their use in tissue engineering and drug delivery.

Molecular and Materials Engineering for Delivery of Peptide Drugs to Treat Type 2 Diabetes.

Type 2 diabetes is exploding globally. Despite numerous treatment options, nearly half of type 2 diabetics are unsuccessful at properly managing the disease, primarily due to a lack of patient compliance, driven by adverse side effects as well as complicated and frequent dosing schedules. Improving the delivery of type 2 diabetes drugs has the potential to increase patient compliance and thus, greatly enhance health outcomes and quality of life. This review focuses on molecular and materials engineering strategies that have been implemented to improve the delivery of peptide drugs to treat type 2 diabetes. Peptide drugs benefit from high potency and specificity but suffer from instability and short half-lives that limit their utility as therapeutics and pose a significant delivery challenge. Several approaches have been developed to improve the availability and efficacy of antidiabetic peptides and proteins in vivo. These methods are reviewed herein and include devices, which sustain the release of peptides in long term, and molecular engineering strategies, which prolong circulation time and slow the release of therapeutic peptides. By optimizing the delivery of these peptides and proteins using these approaches, long-term glucose control can be achieved in type 2 diabetes patients.