Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System.

Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proof-of-concept for the development of a new optimized forming injectable depot based on a tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine peptoid-D-peptide formulation ((Phe)GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated.

Metal Cross-Linked Supramolecular Gel Noodles: Structural Insights and Antibacterial Assessment.

Achieving precise control over gelator alignment and morphology is crucial for crafting tailored materials and supramolecular structures with distinct properties. We successfully aligned the self-assembled micelles formed by a functionalized dipeptide 2NapFF into long 1-D "gel noodles" by cross-linking with divalent metal chlorides. We identify the most effective cross-linker for alignment, enhancing mechanical stability, and imparting functional properties.

Two into one does go: Formulation development of a multipurpose combination vaginal ring releasing dapivirine and metronidazole for prevention of HIV infection and treatment of bacterial vaginosis.

Bacterial vaginosis (BV) is a common but often asymptomatic dysbiosis of the human vagina characterized by an imbalance in the normal vaginal microbiota due to loss of lactobacilli and an overgrowth of certain anaerobic bacteria. While BV itself is not a sexually transmitted infection, it is associated with an increased risk in women of various sexually acquired infections, including human immunodeficiency virus (HIV) infection. There is, therefore, a strong rationale for pursuing new multipurpose products that seek to treat or prevent BV alongside preventing HIV infection.

Enzyme-Triggered l-α/d-Peptide Hydrogels as a Long-Acting Injectable Platform for Systemic Delivery of HIV/AIDS Drugs.

Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organization. Patient adherence to complicated dosage regimens remains a key barrier. There is a need for convenient long-acting formulations that deliver drugs over sustained periods.

Injectable Depot Forming Thermoresponsive Hydrogel for Sustained Intrascleral Delivery of Sunitinib Using Hollow Microneedles.

Age-related macular degeneration is a vision-threatening disorder affecting the posterior segment of the eye. Drug delivery to the posterior segment is challenging owing to the complex anatomical and physiological structure, necessitating monthly injections of antivascular endothelial growth factors. Thermoresponsive hydrogels provide sustained drug delivery and ease of injection, due to their sol-gel transition.

Multicomponent Peptide Hydrogels as an Innovative Platform for Cell-Based Tissue Engineering in the Dental Pulp.

In light of the increasing levels of antibiotic resistance, nanomaterials and novel biologics are urgently required to manage bacterial infections. To date, commercially available self-assembling peptide hydrogels have not been studied extensively for their ability to inhibit micro-organisms relevant to tissue engineering sites such as dental root canals. In this work, we assess the biocompatibility of dental pulp stem/stromal cells with commercially available multicomponent peptide hydrogels.

Unravelling the antimicrobial activity of peptide hydrogel systems: current and future perspectives.

The use of hydrogels has garnered significant interest as biomaterial and drug delivery platforms for anti-infective applications. For decades antimicrobial peptides have been heralded as a much needed new class of antimicrobial drugs. Self-assembling peptide hydrogels with inherent antimicrobial ability have recently come to the fore.

Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections.

Chronic fungal infection of the cornea could lead to blindness if not treated properly. Topical amphotericin B (AMP-B) is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea lead to poor bioavailability.

Ultrashort Peptide Hydrogels Display Antimicrobial Activity and Enhance Angiogenic Growth Factor Release by Dental Pulp Stem/Stromal Cells.

Recent studies on peptide hydrogels have shown that ultrashort peptides (<8 amino acids) can self-assemble into hydrogels. Ultrashort peptides can be designed to incorporate antimicrobial motifs, such as positively charged lysine residues, so that the peptides have inherent antimicrobial characteristics. Antimicrobial hydrogels represent a step change in tissue engineering and merit further investigation, particularly in applications where microbial infection could compromise healing.

Tuning the antimicrobial activity of low molecular weight hydrogels using dopamine autoxidation.

We present a method to trigger the formation of dipeptide-based hydrogels by the simple addition of dopamine. Dopamine undergoes oxidation in air, reducing the pH to induce gelation. The production of polydopamine and release of reactive oxygen species such as hydrogen peroxide confers antimicrobial activity.

High-throughput toxicity screening of novel azepanium and 3-methylpiperidinium ionic liquids.

Ionic liquids (ILs) have been employed as potentially environmentally friendly replacements for harmful organic solvents, but have also been studied for their use in bioelectrochemical applications, such as in microbial electrochemistry for bioenergy production, or in industrial biocatalysis. For these processes, low microbial toxicity is important and there is a growing need for microbial toxicology studies for novel ILs. In this study, we report initial toxicity data for novel ILs, based on azepanium and 3-methylpiperidinium cations.

Pharmaceutical Formulation and Characterization of Dipeptide Nanotubes for Drug Delivery Applications.

Peptide nanotubes are promising materials for a variety of biomedical applications with ultrashort (≤7 amino acids) forms providing particular promise for clinical translation. The manufacture of peptide nanotubes has, however, been associated with toxic organic solvents restricting clinical use. The purpose of this work is to formulate dipeptide nanotubes using mild techniques easily translated to industrial upscale and to characterize their physiochemical and biological properties.

Peptide Nanomaterials for Drug Delivery Applications.

Self-assembled peptides have been shown to form well-defined nanostructures which display outstanding characteristics for many biomedical applications and especially in controlled drug delivery. Such biomaterials are becoming increasingly popular due to routine, standardized methods of synthesis, high biocompatibility, biodegradability and ease of upscale. Moreover, one can modify the structure at the molecular level to form various nanostructures with a wide range of applications in the field of medicine.

Ultrashort Self-Assembling Peptide Hydrogel for the Treatment of Fungal Infections.

The threat of antimicrobial resistance to society is compounded by a relative lack of new clinically effective licensed therapies reaching patients over the past three decades. This has been particularly problematic within antifungal drug development, leading to a rise in fungal infection rates and associated mortality. This paper highlights the potential of an ultrashort peptide, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH), encompassing hydrogel-forming and antifungal properties within a single peptide motif, thus overcoming formulation (e.

Development of a teaching model to advance skills in industrial pharmaceutical formulation and regulatory aspects.

Background And Purpose: To design and critically evaluate a laboratory-scale pharmaceutical formulation practical that enables pharmaceutical science students to develop work-based skills relating to industrial pharmacy such as problem solving, pharmaceutical calculations, research, legal checking, communication, practical aptitude, handling of medicinal products, record keeping, and ability to interpret, analyze and report data.

Educational Activity And Setting: Nine laboratory practical sessions were designed whereby students formulated a range of dosage forms and conducted corrective and preventative actions (CAPAs) exercises. A master batch formula outlined the specifications for each product and a practical sheet was provided for the students to record their activities.

Self-assembling diphenylalanine peptide nanotubes selectively eradicate bacterial biofilm infection.

Unlabelled: Biofilms present a major problem to industry and healthcare worldwide. Composed of a population of surface-attached microbial cells surrounded by a protective extracellular polysaccharide matrix, they are responsible for increased tolerance to antibiotics, treatment failure and a resulting rise in antimicrobial resistance. Here we demonstrate that self-assembled peptide nanostructures composed of a diphenylalanine motif provide sufficient antibacterial activity to eradicate mature biofilm forms of bacteria widely implicated in hospital infections.

Antibiotic susceptibility of planktonic- and biofilm-grown staphylococci isolated from implant-associated infections: should MBEC and nature of biofilm formation replace MIC?

Purpose: The purpose of this study was to develop an alternative, more clinically relevant approach to susceptibility reporting for implant-associated infections. Using 20 staphylococcal isolates, isolated from clinical implant infections, the majority (85 %) demonstrated biofilm-forming capabilities. A significantly increased minimum biofilm eradication concentration (MBEC) compared to minimum inhibitory concentration (MIC) breakpoint was obtained, with MBEC values greater than 256 µg ml-1 for the majority of bacteria.

Ultrashort self-assembling Fmoc-peptide gelators for anti-infective biomaterial applications.

Biomaterial-related infections have a significant impact on society and are a major contributor to the growing threat of antimicrobial resistance. Current licensed antibiotic classes struggle to breakdown or penetrate the exopolysaccharide biofilm barrier, resulting in sub-therapeutic concentrations of antibiotic at the surface of the biomaterial, treatment failure and increased spread of resistant isolates. This paper focuses for the first time on the ability of ultrashort Fmoc-peptide gelators to eradicate established bacterial biofilms implicated in a variety of medical device infections (Gram-positive: Staphylococcus aureus, Staphylococcus epidermidis and Gram-negative Escherichia coli, Pseudomonas aeruginosa).

Peptide Therapeutics and the Pharmaceutical Industry: Barriers Encountered Translating from the Laboratory to Patients.

Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages.

Potential strategies for the eradication of multidrug-resistant Gram-negative bacterial infections.

Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding.

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner.

Developing Entrepreneurial Skills in Pharmacy Students.

Objective. To create, implement, and evaluate a workshop that teaches undergraduate pharmacy students about entrepreneurship. Design.

Anti-biofilm activity of ultrashort cinnamic acid peptide derivatives against medical device-related pathogens.

The threat of antimicrobial resistance has placed increasing emphasis on the development of innovative approaches to eradicate multidrug-resistant pathogens. Biofilm-forming microorganisms, for example, Staphylococcus epidermidis and Staphylococcus aureus, are responsible for increased incidence of biomaterial infection, extended hospital stays and patient morbidity and mortality. This paper highlights the potential of ultrashort tetra-peptide conjugated to hydrophobic cinnamic acid derivatives.