Intranasal delivery of glucagon-like peptide-1 to the brain for obesity treatment: opportunities and challenges.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), approved by the US FDA for obesity treatment, are typically administered subcutaneously, an invasive method leading to suboptimal patient adherence and peripheral side effects. Additionally, this route requires the drug to cross the restrictive blood-brain barrier (BBB), limiting its safety and effectiveness in weight management and cognitive addiction disorders. Delivering the drug intranasally could overcome these drawbacks.

Liposomes for Inhalation.

Inhalation of liposomes formulated with phospholipids similar to endogenous lung surfactants and lipids offers biocompatibility and versatility within the pulmonary medicine field to treat a range of diseases such as lung cancer, cystic fibrosis and lung infections. Manipulation of the physicochemical properties of liposomes enables innovative design of the carrier to meet specific delivery, release and targeting requirements. This delivery system offers several benefits: improved pharmacokinetics with reduced toxicity, enhanced therapeutic efficacy, increased delivery of poorly soluble drugs, taste masking, biopharmaceutics degradation protection and targeted cellular therapy.

Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2.

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder.

Insulin Delivery to the Brain via the Nasal Route: Unraveling the Potential for Alzheimer's Disease Therapy.

This comprehensive review delves into the potential of intranasal insulin delivery for managing Alzheimer's Disease (AD) while exploring the connection between AD and diabetes mellitus (DM). Both conditions share features of insulin signalling dysregulation and oxidative stress that accelerate inflammatory response. Given the physiological barriers to brain drug delivery, including the blood-brain barrier, intranasal administration emerges as a non-invasive alternative.

An overview of in vitro and in vivo techniques for characterization of intranasal protein and peptide formulations for brain targeting.

The surge in neurological disorders necessitates innovative strategies for delivering active pharmaceutical ingredients to the brain. The non-invasive intranasal route has emerged as a promising approach to optimize drug delivery to the central nervous system by circumventing the blood-brain barrier. While the intranasal approach offers numerous advantages, the lack of a standardized protocol for drug testing poses challenges to both in vitro and in vivo studies, limiting the accurate interpretation of nasal drug delivery and pharmacokinetic data.

Oscillating high aspect ratio micro-channels can effectively atomize liquids into uniform aerosol droplets and dial their size on-demand.

Ultrasonic atomization of liquids into micrometer-diameter droplets is crucial across multiple fields, ranging from drug delivery, to spectrometry and printing. Controlling the size and uniformity of the generated droplets on-demand is crucial in all these applications. However, existing systems lack the required precision to tune the droplet properties, and the underlying droplet formation mechanism under high-frequency ultrasonic actuation remains poorly understood due to experimental constraints.

Canister valve and actuator deposition in metered dose inhalers formulated with low-GWP propellants.

A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces. Wall-material interactions differ between transparent vials used for visual inspection and metal canister pMDI systems. This is of particular concern for low greenhouse warming potential (GWP) formulations where propellant chemistry and solubility with many drugs are not well understood.

Challenges and current advances in in vitro biofilm characterization.

Biofilms are structured communities of bacterial cells encased in a self-produced polymeric matrix, which develop over time and exhibit temporal responses to stimuli from internal biological processes or external environmental changes. They can be detrimental, threatening public health and causing economic loss, while they also play beneficial roles in ecosystem health, biotechnology processes, and industrial settings. Biofilms express extreme heterogeneity in their physical properties and structural composition, resulting in critical challenges in understanding them comprehensively.

Advances in soft mist inhalers.

Introduction: Soft mist inhalers (SMIs) are propellant-free inhalers that utilize mechanical power to deliver single or multiple doses of inhalable drug aerosols in the form of a slow mist to patients. Compared to traditional inhalers, SMIs allow for a longer and slower release of aerosol with a smaller ballistic effect, leading to a limited loss in the oropharyngeal area, whilst requiring little coordination of actuation and inhalation by patients. Currently, the Respimat® is the only commercially available SMI, with several others in different stages of preclinical and clinical development.

Molecular Characterization and Phylogenetic Analysis of () of () Isolates in Central State of Peninsular Malaysia.

, the etiological agent of Glässer's disease, is an economically significant pathogen commonly associated with serofibrinous polyserositis, arthritis, fibrinous bronchopneumonia and/or meningitis. This study is the first attempt to molecularly characterize and provide a detailed overview of the genetic variants of present in Malaysia, in reference to its serotype, virulence-associated trimeric autotransporters () gene and outer membrane protein P2 () gene. The isolates ( = 11) from clinically sick field samples collected from two major pig producing states (Selangor and Perak) were selected for analysis.

The development of a 3D-printed in vitro integrated oro-pharyngeal air-liquid interface cellular throat model for drug transport.

To simulate the deposition of drugs in the oro-pharynx region, several in vitro models are available such as the United States Pharmacopeia-Induction Port (USP-IP) throat and the Virginia Commonwealth University (VCU) models. However, currently, there is no such in vitro model that incorporates a biological barrier to elucidate drug transport across the pharyngeal cells. Cellular models such as in vitro air-liquid interface (ALI) models of human respiratory epithelial cell lines are extensively used to study drug transport.

Microfluidics assembly of inhalable liposomal ciprofloxacin characterised by an innovative in vitro pulmonary model.

Respiratory tract infections (RTIs) are reported to be the leading cause of death worldwide. Delivery of liposomal antibiotic nano-systems via the inhalation route has drawn significant interest in RTIs treatment as it can directly target the site of infection and reduces the risk of systemic exposure and side effects. Moreover, this formulation system can improve pharmacokinetics and biodistribution and enhance the activity against intracellular pathogens.

Development of Inhalable Spray Dried Nitrofurantoin Formulations for the Treatment of Emphysema.

A central characteristic of emphysematous progression is the continuous destruction of the lung extracellular matrix (ECM). Current treatments for emphysema have only addressed symptoms rather than preventing or reversing the loss of lung ECM. Nitrofurantoin (NF) is an antibiotic that has the potential to induce lung fibrosis as a side effect upon oral administration.

In vitro interactions of aerosol formulations with human nasal epithelium using real-time monitoring of drug transport in a nasal mucosa-on-a-chip.

The current organ-on-chip platforms used for studying respiratory drug delivery are limited to the administration of drug solutions and suspensions, lacking the in vivo aerosol drug administration and aerosol interaction with the respiratory tract barrier. Moreover, they mostly rely on conventional assays that require sample collection and 'off the chip' analyses, which can be labor-intensive and costly. In this study, a human nasal epithelial mucosa (NEM)-on-a-chip is developed that enables the deposition of aerosolized nasal formulations while emulating realistic shear stresses (0.

Real-time in-situ electrochemical monitoring of Pseudomonas aeruginosa biofilms grown on air-liquid interface and its antibiotic susceptibility using a novel dual-chamber microfluidic device.

Biofilms are communities of bacterial cells encased in a self-produced polymeric matrix that exhibit high tolerance toward environmental stress. Despite the plethora of research on biofilms, most P. aeruginosa biofilm models are cultured on a solid-liquid interface, and the longitudinal growth characteristics of P.

evaluation of nebulized eucalyptol nano-emulsion formulation as a potential COVID-19 treatment.

Coronavirus is a type of acute atypical respiratory disease representing the leading cause of death worldwide. Eucalyptol (EUC) known also as 1,8-cineole is a potential inhibitor candidate for COVID-19 (main protease-M) with effective antiviral properties but undergoes physico-chemical instability and poor water solubility. Nano-emulsion (NE) is a promising drug delivery system to improve the stability and efficacy of drugs.

Thermoresponsive and Injectable Hydrogel for Tissue Agnostic Regeneration.

Injectable hydrogels can support the body's innate healing capability by providing a temporary matrix for host cell ingrowth and neovascularization. The clinical adoption of current injectable systems remains low due to their cumbersome preparation requirements, device malfunction, product dislodgment during administration, and uncontrolled biological responses at the treatment site. To address these challenges, a fully synthetic and ready-to-use injectable biomaterial is engineered that forms an adhesive hydrogel that remains at the administration site regardless of defect anatomy.

Protective Abilities of an Inhaled DPI Formulation Based on Sodium Hyaluronate against Environmental Hazards Targeting the Upper Respiratory Tract.

The exposure of lung epithelium to environmental hazards is linked to several chronic respiratory diseases. We assessed the ability of an inhaled dry powder (DPI) medical device product (PolmonYDEFENCE/DYFESA, SOFAR SpA, Trezzano Rosa, Italy), using a formulation of sodium hyaluronate (Na-Hya) as the key ingredient as a defensive barrier to protect the upper respiratory tract. Specifically, it was evaluated if the presence of the barrier formed by sodium hyaluronate present on the cells, reducing direct contact of the urban dust (UD) with the surface of cells can protect them in an indirect manner by the inflammatory and oxidative process started in the presence of the UD.

Validation of a cell integrated next-generation impactor to assess in vitro drug transport of physiologically relevant aerosolised particles.

The development of novel inhaled formulations in the pre-clinical stage has been impeded by a lack of meaningful information related to drug dissolution and transport at the lung epithelia due to the absence of physiologically relevant in vitro respiratory models. The objective of the present study was to develop an in vitro experimental model, which combined the next generation impactor (NGI) and two respiratory epithelial cell lines, for examining the aerodynamic performance of dry powder inhalers and the fate of aerosolised drugs following lung deposition. The NGI impaction plates of stage 3 (i.

Investigating potential TRPV1 positive feedback to explain TRPV1 upregulation in airway disease states.

Objective: The airway epithelium is a potential source of pathophysiology through activation of transient potential receptor vallinoid type 1 (TRPV1) channel. A positive feedback cycle caused by TRPV1 activity is hypothesized to induce upregulation and production of inflammatory cytokines, leading to exacerbations of chronic airway diseases. These cytokine and protein regulation effects were investigated in this study.

Engineered nasal dry powder for the encapsulation of bioactive compounds.

In this review, we present the potential of nasal dry powders to deliver stable bioactive compounds and their manufacture using spray-drying (SD) techniques to achieve encapsulation. We also review currently approved and experimental excipients used for powder manufacturing for specific target drugs. Polymers, sugars, and amino acids are recommended for specific actions, such as mucoadhesive interactions, to increase residence time on the nasal mucosa; for example, high-molecular weight polymers, such as hydroxypropyl methylcellulose, or mannitol, which protect the bioactive compounds, increase their stability, and enhance drug absorption in the nasal mucosa; and leucine, which promotes particle formation and improves aerosol performance.

Application of Micro-Engineered Kidney, Liver, and Respiratory System Models to Accelerate Preclinical Drug Testing and Development.

Developing novel drug formulations and progressing them to the clinical environment relies on preclinical in vitro studies and animal tests to evaluate efficacy and toxicity. However, these current techniques have failed to accurately predict the clinical success of new therapies with a high degree of certainty. The main reason for this failure is that conventional in vitro tissue models lack numerous physiological characteristics of human organs, such as biomechanical forces and biofluid flow.

The application of in vitro cellular assays for analysis of electronic cigarettes impact on the airway.

Electronic (e)-cigarettes have been marketed for more than a decade as an alternative to conventional cigarettes. Their popularity and use among adolescents have grown significantly during recent years. While e-cigarettes do not release carcinogenic aromatic hydrocarbons, they can generate reactive carbonyls and radicals during the heating process in vitro.

Understanding the effects of aerodynamic and hydrodynamic shear forces on Pseudomonas aeruginosa biofilm growth.

Biofilms are communities of bacterial cells encased in a self-produced polymeric matrix and exhibit high tolerance towards environmental stress. Despite the plethora of research on biofilms, most biofilm models are produced using mono-interface culture in static flow conditions, and knowledge of the effects of interfaces and mechanical forces on biofilm development remains fragmentary. This study elucidated the effects of air-liquid (ALI) or liquid-liquid (LLI) interfaces and mechanical shear forces induced by airflow and hydrodynamic flow on biofilm growing using a custom-designed dual-channel microfluidic platform.

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract.

Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed.