Methacrylated poly(glycerol sebacate) as a photocurable, biocompatible, and biodegradable polymer with tunable degradation and drug release kinetics.

Poly(glycerol sebacate) (PGS) is a biodegradable, elastomeric polymer that has been explored for applications including tissue engineering, drug delivery, and wound repair. Despite its promise, its biomedical utility is limited by its rapid, and largely fixed, degradation rate. Additionally, its preparation requires prolonged curing at high temperatures, rendering it incompatible with heat-sensitive molecules, complex device geometries, and high-throughput production.

Intra-lymph node crosslinking of antigen-bearing polymers enhances humoral immunity and dendritic cell activation.

Lymph node (LN)-resident dendritic cells (DCs) are a promising target for vaccination given their professional antigen-presenting capabilities and proximity to a high concentration of immune cells. Direct intra-LN injection has been shown to greatly enhance the immune response to vaccine antigens compared to traditional intramuscular injection, but it is infeasible to implement clinically in a vaccination campaign context. Employing the passive lymphatic flow of antigens to target LNs has been shown to increase total antigen uptake by DCs more than inflammatory adjuvants, which recruit peripheral DCs.

Probing the Effects of Chirality on Self-Assembling Peptides: Hydrogel Formation, Degradation, Antigen Release, and Adjuvancy.

Introduction: Multidomain peptides (MDPs) are amino acid sequences that self-assemble to form supramolecular hydrogels under physiological conditions that have shown promise for a number of biomedical applications. K(SL)K ("K"), a widely studied MDP, has demonstrated the ability to enhance the humoral immune response to co-delivered antigen. Herein, we sought to explore the in vitro and in vivo properties of a peptide with the same sequence but opposite chirality (D-K) since peptides composed of D-amino acids are resistant to protease degradation and potentially more immunostimulatory than their canonical counterparts.

A TLR7 Agonist Conjugated to a Nanofibrous Peptide Hydrogel as a Potent Vaccine Adjuvant.

Toll-like receptors (TLRs) recognize pathogen- and damage-associated molecular patterns and, in turn, trigger the release of cytokines and other immunostimulatory molecules. As a result, TLR agonists are increasingly being investigated as vaccine adjuvants. Many of these agonists are small molecules that quickly diffuse away from the vaccination site, limiting their co-localization with antigens and, thus, their effect.

A TLR7 Agonist Conjugated to a Nanofibrous Peptide Hydrogel as a Potent Vaccine Adjuvant.

Unlabelled: Toll-like receptors (TLRs) recognize pathogen- and damage-associated molecular patterns and, in turn, trigger the release of cytokines and other immunostimulatory molecules. As a result, TLR agonists are increasingly being investigated as vaccine adjuvants, though many of these agonists are small molecules that quickly diffuse away from the vaccination site, limiting their co-localization with antigens and, thus, their effect. Here, the small-molecule TLR7 agonist 1V209 is conjugated to a positively-charged multidomain peptide (MDP) hydrogel, K , which was previously shown to act as an adjuvant promoting humoral immunity.

Methacrylated poly(glycerol sebacate) as a photocurable, biocompatible, and biodegradable polymer with tunable degradation and drug release kinetics.

Poly(glycerol sebacate) (PGS) is a biodegradable, elastomeric polymer that has been explored for applications ranging from tissue engineering to drug delivery and wound repair. Despite its promise, its biomedical utility is limited by its rapid, and largely fixed, degradation rate. Additionally, its preparation requires high temperatures for long periods of time, rendering it incompatible with heat-sensitive molecules, complex device geometries, and high-throughput production.

Multidomain peptide hydrogel adjuvants elicit strong bias towards humoral immunity.

Adjuvants play a critical role in enhancing vaccine efficacy; however, there is a need to develop new immunomodulatory compounds to address emerging pathogens and to expand the use of immunotherapies. Multidomain peptides (MDPs) are materials composed of canonical amino acids that form injectable supramolecular hydrogels under physiological salt and pH conditions. MDP hydrogels are rapidly infiltrated by immune cells and have previously been shown to influence cytokine production.

Zero-order drug delivery: State of the art and future prospects.

Pharmaceutical drugs are an important part of the global healthcare system, with some estimates suggesting over 50% of the world's population takes at least one medication per day. Most drugs are delivered as immediate-release formulations that lead to a rapid increase in systemic drug concentration. Although these formulations have historically played an important role, they can be limited by poor patient compliance, adverse side effects, low bioavailability, or undesirable pharmacokinetics.