Cucurbit[n]urils as excipients in pharmaceutical dosage forms

Native, unfunctionalised cucurbit[n]urils (n = 6, 7, or 8) have shown enormous potential as excipients in medical formulations for improving drug delivery. Specific benefits include improved drug stability, solubility, controlled or triggered release, taste masking, inducing drug pKa shifts and as antidotes. Base on in vitro and in vivo models, cucurbit[n]urils have been found to have little systemic toxicity, although they do show some specific organ toxicity, and appear to not affect developmental biology. Cucurbit[n]urils readily form hydrates in the solid state, which leads to pseudo-crystal polymorphs that can ultimately affect cucurbit[n]uril–drug complex solubility, bioavailability and through these drug effectiveness. In creating cucurbit[n]uril-based dosage forms, it has been found that the macrocycles can interact with other excipients in the formulation in both the solid state and solution. While the nature of the solid-state interactions are unclear, several studies of solutions have shown that some excipients are incompatible with cucurbit[n]urils as they can cause precipitates and will compete with the drugs for binding within the cavity. To date, cucurbit[n]urils have been formulated into five different dosage forms: oral solid tablet, topical cream, eye drop, implantable hydrogel and nasal insert.Ni

Quantum Dot Nanomedicine Formulations Dramatically Improve Pharmacological Properties and Alter Uptake Pathways of Metformin and Nicotinamide Mononucleotide in Aging Mice

Orally administered Ag2S quantum dots (QDs) rapidly cross the small intestine and are taken up by the liver. Metformin and nicotinamide mononucleotide (NMN) target metabolic and aging processes within the liver. This study examined the pharmacology and toxicology of QD-based nanomedicines as carriers of metformin and NMN in young and old mice, determining if their therapeutic potency and reduced effects associated with aging could be improved. Pharmacokinetic studies demonstrated that QD-conjugated metformin and NMN have greater bioavailability, with selective accumulation in the liver following oral administration compared to unconjugated formulations. Pharmacodynamic data showed that the QD-conjugated medicines had increased physiological, metabolic, and cellular potency compared to unconjugated formulations (25× metformin; 100× NMN) and highlighted a shift in the peak induction of, and greater metabolic response to, glucose tolerance testing. Two weeks of treatment with low-dose QD-NMN (0.8 mg/kg/day) improved glucose tolerance tests in young (3 months) mice, whereas old (18 and 24 months) mice demonstrated improved fasting and fed insulin levels and insulin resistance. High-dose unconjugated NMN (80 mg/kg/day) demonstrated improvements in young mice but not in old mice. After 100 days of QD (320 μg/kg/day) treatment, there was no evidence of cellular necrosis, fibrosis, inflammation, or accumulation. Ag2S QD nanomedicines improved the pharmacokinetic and pharmacodynamic properties of metformin and NMN by increasing their therapeutic potency, bypassing classical cellular uptake pathways, and demonstrated efficacy when drug alone was ineffective in aging mice

Gallium nanoparticle as an antimicrobial agent to combat antibiotic resistance

Since they were first discovered, antibiotics have been used to fight bacterial infections and save millions of lives. However, their increased use has allowed for the development of antibiotic resistant pathogens, which reduces their efficacy and threatens the accomplishments of modern medicine. The development of a new agent represents a major unmet clinical societal need. Metals are increasingly becoming considered as an alternative antimicrobial agent, and gallium in particular has gained a lot of attention in recent years. Whilst their antimicrobial activity has been demonstrated against a variety of bacterial pathogens and biofilms, their translation into the clinical setting is partly hindered by its low bioavailability. To address this issue, this project aimed to use nanotechnology to develop gallium-based nano-formulations. Several synthesis methods, namely the heat-up method, hot-injection and flame spray pyrolysis were successfully used to synthesise different classes of gallium nanoparticle. The heat-up method produced gallium nanoparticles with low uniformity and was difficult to reproduce. As such, only hot-injection and flame spray pyrolysis synthesised gallium nanoparticles were further investigated for their antimicrobial activity and toxicity. Despite undetected minimum inhibitory concentrations, gallium nanoparticles showed activity towards biofilm. They altered biofilm morphology and reduced pyocyanin production, which relates to the pathogen’s virulence factor. The results indicate the potential of gallium nanoparticle for development as an antimicrobial agen

Synthesis of Antimicrobial Gallium Nanoparticles Using the Hot Injection Method

Antibiotic resistance continues to be an ongoing problem in global public health despite interventions to reduce antibiotic overuse. Furthermore, it threatens to undo the achievements and progress of modern medicine. To address these issues, the development of new alternative treatments is needed. Metallic nanoparticles have become an increasingly attractive alternative due to their unique physicochemical properties that allow for different applications and their various mechanisms of action. In this study, gallium nanoparticles (Ga NPs) were tested against several clinical strains of Pseudomonas aeruginosa (DFU53, 364077, and 365707) and multi-drug-resistant Acinetobacter baumannii (MRAB). The results showed that Ga NPs did not inhibit bacterial growth when tested against the bacterial strains using a broth microdilution assay, but they exhibited effects in biofilm production in P. aeruginosa DFU53. Furthermore, as captured by atomic force microscopy imaging, P. aeruginosa DFU53 and MRAB biofilms underwent morphological changes, appearing rough and irregular when they were treated with Ga NPs. Although Ga NPs did not affect planktonic bacterial growth, their effects on both biofilm formation and established biofilm demonstrate their potential role in the race to combat antibiotic resistance, especially in biofilm-related infections

Placenta stem/stromal cell-derived extracellular vesicles for potential use in lung repair

Many acute and chronic lung injuries are incurable and rank as the fourth leading cause of death globally. While stem cell treatment for lung injuries is a promising approach, there is growing evidence that the therapeutic efficacy of stem cells originates from secreted extracellular vesicles (EVs). Consequently, EVs are emerging as next‐generation therapeutics. While EVs are extensively researched for diagnostic applications, their therapeutic potential to promote tissue repair is not fully elucidated. By housing and delivering tissue‐repairing cargo, EVs refine the cellular microenvironment, modulate inflammation, and ultimately repair injury. Here, the potential use of EVs derived from two placental mesenchymal stem/stromal cell (MSC) lines is presented; a chorionic MSC line (CMSC29) and a decidual MSC cell line (DMSC23) for applications in lung diseases. Functional analyses using in vitro models of injury demonstrate that these EVs have a role in ameliorating injuries caused to lung cells. It is also shown that EVs promote repair of lung epithelial cells. This study is fundamental to advancing the field of EVs and to unlock the full potential of EVs in regenerative medicine