Computational study of the impact of nasal vestibule anatomy on nasal drug administration with nasal spray.

The nasal airway comprises a complex network of passages and chambers and plays an important role in regulating the respiratory system's functions. The nasal vestibule is the first chamber of the nasal airway. While variations in nasal vestibule geometries are known to exist between humans, details of their implications on how they may affect the efficacy of nasal drug delivery devices are less clear.

Chronoamperometric interrogation of an electrochemical aptamer-based sensor with tetrahedral DNA nanostructure pendulums for continuous biomarker measurements.

Tetrahedral DNA nanostructure (TDN) is highly promising in developing electrochemical aptamer-based (E-AB) sensors for biomolecular detection, owing to its inherit programmability, spatial orientation and structural robustness. However, current interrogation strategies applied for TDN-based E-AB sensors, including enzyme-based amperometry, voltammetry, and electrochemical impedance spectroscopy, either require complicated probe design or suffer from limited applicability or selectivity. In this study, a TDN pendulum-empowered E-AB sensor interrogated by chronoamperometry for reagent-free and continuous monitoring of a blood clotting enzyme, thrombin, was developed.

Numerical and experimental evaluation of nasopharyngeal aerosol administration methods in children with adenoid hypertrophy.

Administering aerosol drugs through the nasal pathway is a common early treatment for children with adenoid hypertrophy (AH). To enhance therapeutic efficacy, a deeper understanding of nasal drug delivery in the nasopharynx is essential. This study uses an integrated experimental, numerical modelling approach to investigate the delivery process of both the aerosol mask delivery system (MDS) and the bi-directional delivery system (BDS) in the pediatric nasal airway with AH.

Understanding the effects of inhaler resistance on particle deposition behaviour - A computational modelling study.

Background And Objective: Understanding the impact of inhaler resistance on particle transport and deposition in the human upper airway is essential for optimizing inhaler designs, thereby contributing to the enhancement of the therapeutic efficacy of inhaled drug delivery. This study demonstrates the potential effects of inhaler resistance on particle deposition characteristics in an anatomically realistic human oropharynx and the United States Pharmacopeia (USP) throat using computational fluid dynamics (CFD).

Method: Magnetic resonance (MR) imaging was performed on a healthy volunteer biting on a small mockup inhaler mouthpiece.

Numerical analysis of airflow and particle deposition in multi-fidelity designs of nasal replicas following nasal administration.

Background And Objective: An improved understanding of flow behaviour and particle deposition in the human nasal airway is useful for optimising drug delivery and assessing the implications of pollutants and toxin inhalation. The geometry of the human nasal cavity is inherently complex and presents challenges and manufacturing constraints in creating a geometrically realistic replica. Understanding how anatomical structures of the nasal airway affect flow will shed light on the mechanics underpinning flow regulation in the nasal pharynx and provide a means to interpret flow and particle deposition data conducted in a nasal replica or model that has reduced complexity in terms of their geometries.

A pendulum-type electrochemical aptamer-based sensor for continuous, real-time and stable detection of proteins.

Continuous detection of proteins is crucial for health management and biomedical research. Electrochemical aptamer-based (E-AB) sensor that relies on binding affinity between a recognition oligonucleotide and its specific target is a versatile platform to fulfill this purpose. Yet, the vast majority of E-AB sensors are characterized by voltammetric methods, which suffer from signal drifts and low-frequency data acquisition during continuous operations.

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.

Challenges in the Development and Application of Organ-on-Chips for Intranasal Drug Delivery Studies.

With the growing demand for the development of intranasal (IN) products, such as nasal vaccines, which has been especially highlighted during the COVID-19 pandemic, the lack of novel technologies to accurately test the safety and effectiveness of IN products in vitro so that they can be delivered promptly to the market is critically acknowledged. There have been attempts to manufacture anatomically relevant 3D replicas of the human nasal cavity for in vitro IN drug tests, and a couple of organ-on-chip (OoC) models, which mimic some key features of the nasal mucosa, have been proposed. However, these models are still in their infancy, and have not completely recapitulated the critical characteristics of the human nasal mucosa, including its biological interactions with other organs, to provide a reliable platform for preclinical IN drug tests.

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.

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.

Quantifying Agglomerate-to-Wall Impaction in Dry Powder Inhalers.

Purpose: The probability of agglomerate-to-wall collision was quantified using a unique image processing technique applied to high-speed microscopic images. The study aimed to investigate the effects of flow rate and particle size on the percentage of colliding agglomerates detected within an in-house powder dispersion device.

Method: The device consists of a swirl chamber and two tangential inlets in various configurations, designed to emulate the geometric features of commercial devices such as the Aerolizer® and Osmohaler®.

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.

Simulating the effect of individual upper airway anatomical features on drug deposition.

This study aims to systematically isolate different anatomical features of the human pharynx with the goal to investigate their independent influence on airflow dynamics and particle deposition characteristics in a geometrically realistic human airway. Specifically, the effects of the uvula, epiglottis and soft palate on drug particle deposition are studied systematically, by carefully removing each of these anatomical features from reconstructed models based on MRI data and comparing them to a benchmark realistic airway model. Computational Fluid Dynamics using established turbulence models is employed to simulate the transport of mono-dispersed particles (3 µm) in the airway at two flow-rates.

A review of upper airway physiology relevant to the delivery and deposition of inhalation aerosols.

Developing effective oral inhaled drug delivery treatment strategies for respiratory diseases necessitates a thorough knowledge of the respiratory system physiology, such as the differences in the airway channel's structure and geometry in health and diseases, their surface properties, and mechanisms that maintain their patency. While respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma and their implications on the lower airways have been the core focus of most of the current research, the role of the upper airway in these diseases is less known, especially in the context of inhaled drug delivery. This is despite the fact that the upper airway is the passageway for inhaled drugs to be delivered to the lower airways, and their replicas are indispensable in current standards, such as the cascade impactor experiments for testing inhaled drug delivery technology.

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.

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.

Effects of respiratory rate on the fluid mechanics of a reconstructed upper airway.

This study aims to utilise particle image velocimetry (PIV) techniques to investigate the time-dependant effects of respiratory rate in the extrathoracic airway, to show how they affect the flow field developed. There has been limited validation of computational fluid dynamics (CFD) models using experimental setups. Furthermore, the large majority of existing CFD models focus on rigid airways, not accounting for active deformation through the breathing cycle.

From laminar to turbulent flow in a dry powder inhaler: The effect of simple design modifications.

In order to better understand powder dispersion in dry powder inhaler (DPI) devices, a new powder disperser was designed, which uses flow modifiers to alter powder fluidization behavior so as to physically replicate various flow conditions observed in a range of commercial DPIs. The influence of these modifiers on the performance of the DPI was analyzed for flowrates progressing from laminar (15 L/min) to transitional (30 L/min), and finally turbulent flow regimes (60 L/min) in the device. The aerosol performance of the disperser was measured using a Next Generation Impactor.

An adaptable microreactor to investigate the influence of interfaces on Pseudomonas aeruginosa biofilm growth.

Biofilms are ubiquitous and notoriously difficult to eradicate and control, complicating human infections and industrial and agricultural biofouling. However, most of the study had used the biofilm model that attached to solid surface and developed in liquid submerged environments which generally have neglected the impact of interfaces. In our study, a reusable dual-chamber microreactor with interchangeable porous membranes was developed to establish multiple growth interfaces for biofilm culture and test.

Effect of inflow conditioning for dry powder inhalers.

The transport of pharmaceutical dry powder inside an optically accessible inhaler-like device is studied using both macro- and microscopic high-speed imaging. The investigation aims to systematically study the effect of inflow modifications on the dispersion characteristics of agglomerates inside a dry powder inhaler (DPI) geometry. An inhaler device was designed with geometrical features akin to commercial inhalers used in the current market and research oriented inhalers such as the Twincer®: two offset inlet channels (one with a powder pocket), a clockwise swirling chamber and a single outlet channel.

Real-time quantitative monitoring of nasal drug delivery by a nasal epithelial mucosa-on-a-chip model.

Objectives: A human nasal epithelial mucosa (NEM) on-a-chip is developed integrated with a novel carbon nanofibers-modified carbon electrode for real-time quantitative monitoring of nasal drug delivery. The integration of platinum electrodes in the chip also enables real-time measurement of transepithelial electrical resistance (TEER).

Methods: The air-liquid interface culture of nasal epithelial RPMI 2650 cells in the NEM-on-a-chip was optimized to mimic the key functional characteristics of the human nasal mucosa.

Mechanical properties of single cells: Measurement methods and applications.

Cell mechanical properties, e.g. elastic and shear modulus, play vital roles in cell activities and functions, such as cell growth, cell division, cell motion, and cell adhesion.

Non-intrusive high resolution in-vitro measurement of regional drug powder deposition.

Optical Coherence Tomography (OCT) is a high-resolution and non-invasive cross-sectional imaging technique mainly used for medical imaging and industrial non-destructive testing. However, its feasibility in the quantification of pulmonary drug deposition has not been investigated. In this study, an optically accessible airway model of the upper airway and the tracheobronchial tree was used, and experiments were performed at flow rates of 40 L/min, 60 L/min and 80 L/min.

The effects of upper airway tissue motion on airflow dynamics.

The human upper airway is not only geometrically complex, but it can also deform dynamically as a result of active muscle contraction and motility during respiration. How the active transformation of the airway geometry affects airflow dynamics during respiration is not well understood despite the importance of this knowledge towards improving current understanding of particle transport and deposition. In this study, particle imaging velocimetry (PIV) measurements of the fluid dynamics are presented in a physiologically realistic human upper airway replica for (i) the undeformed case and (ii) the case where realistic soft tissue motion during breathing is emulated.