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.

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.

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.

Engineered dry powders for the nose-to-brain delivery of transforming growth factor-beta.

Nose-to-brain delivery is increasing in popularity as an alternative to other invasive delivery routes. However, targeting the drugs and bypassing the central nervous system are challenging. We aim to develop dry powders composed of nanoparticles-in-microparticles for high efficiency of nose-to-brain delivery.

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.

In vitro and in vivo applications of a universal and synthetic thermo-responsive drug delivery hydrogel platform.

A synthetic and thermo-responsive polymer, poly(N-isopropylacrylamide)-co-(polylactide/2-hydroxy methacrylate)-co-(oligo (ethylene glycol)), is used to formulate a universal carrier platform for sustained drug release. The enabling carrier, denoted as TP, is prepared by dissolving the polymer in an aqueous solution at a relatively neutral pH. A wide range of therapeutic moieties can be incorporated without the need for the addition of surfactants, organic solvents, and other reagents to the carrier system.

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.

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.

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.

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.

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.

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.

Does upper airway deformation affect drug deposition?

Knowledge that enables the accurate simulation of drug deposition in the human upper airway is necessary to develop robust platforms for efficient drug delivery by inhalation devices. The human upper airway is deformable during inhalation but how it could affect the deposition of inhaled drugs is unknown. We aimed to determine whether pharyngeal deformation at the soft palate level would have any significant effects on throat deposition, in vitro lung dose and fine particle fraction.

Application of a Thermosensitive In Situ Gel of Chitosan-Based Nasal Spray Loaded with Tranexamic Acid for Localised Treatment of Nasal Wounds.

The integrity of the nasal epithelium plays a crucial role in the airway defence mechanism. The nasal epithelium may be injured as a result of a large number of factors leading to nose bleeds, also known as epistaxis. However, local measures commonly used to treat epistaxis and improve wound healing present several side effects and patient discomfort.

Smart thermosensitive chitosan hydrogel for nasal delivery of ibuprofen to treat neurological disorders.

Background: The in-situ gelation of thermosensitive nasal formulations with desirable spray characteristics at room temperature and ability to undergo a phase change to a semi-solid state with mucoadhesive behavior at physiological temperature has the potential to efficiently deliver therapeutics to brain. However, their application in nasal spray generation with favorable characteristics has not been investigated.

Methods: Thermosensitive chitosan (CS)-based formulations with different viscosities were prepared for intranasal delivery of ibuprofen using CS of various molecular weights.