The understanding of complex inhalation and transport processes of pollutant particles through the human respiratory system is important for investigations into dosimetry and respiratory health effects in various settings, such as environmental or occupational health. The studies over the last few decades for micro- and nanoparticle transport and deposition have advanced the understanding of drug-aerosol impacts in the mouth-throat and the upper airways. However, most of the Lagrangian and Eulerian studies have utilized the non-realistic symmetric anatomical model for airflow and particle deposition predictions. Recent improvements to visualization techniques using high-resolution computed tomography (CT) data and the resultant development of three dimensional (3-D) anatomical models support the realistic representation of lung geometry. Yet, the selection of different modelling approaches to analyze the transitional flow behavior and the use of different inlet and outlet conditions provide a dissimilar prediction of particle deposition in the human lung. Moreover, incorporation of relevant physical and appropriate boundary conditions are important factors to consider for the more accurate prediction of transitional flow and particle transport in human lung. This review critically appraises currently available literature on airflow and particle transport mechanism in the lungs, as well as numerical simulations with the aim to explore processes involved. Numerical studies found that both the Euler–Lagrange (E-L) and Euler–Euler methods do not influence nanoparticle (particle diameter ≤50 nm) deposition patterns at a flow rate ≤25 L/min. Furthermore, numerical studies demonstrated that turbulence dispersion does not significantly affect nanoparticle deposition patterns. This critical review aims to develop the field and increase the state-of-the-art in human lung modelling.

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 behaviour at physiological temperature has the potential to efficiently deliver therapeutics to brain. Although such thermosensitive polymeric nasal formulations have been well studied in the literature for their thermogelling properties, their application in nasal spray generation with favourable 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. The formulation developed was optimized with regards to its physicochemical, rheological, biological properties and the generated aerosol characteristics. Results: The formulations showed rapid gelation (4 – 7 min) at 30 – 35°C, which lies in the human nasal cavity temperature spectrum. The decrease in CS molecular weight to 110 – 150 kDa led to generation of optimum spray with lower Dv₅₀, wider spray area, and higher surface area coverage. This formulation also showed improved ibuprofen solubility that is approximately 100X higher than its intrinsic aqueous solubility, accelerated ibuprofen transport across human nasal epithelial cells and transient modulation of tight junctions. Conclusions: A thermosensitive CS-based formulation has been successfully developed with suitable rheological properties, aerosol performance and biological properties that is beneficial for nose-to-brain drug delivery.

Introduction: The Calu-3 lung cell line has been shown to be a promising in vitro model of airway epithelia due to its similarity to in vivo physiology. Hence, over the past decade, it has found increasing applications in the pharmaceutical industry. Areas covered: This review focuses on the pharmaceutical applications of the Calu-3 cell line in areas such as mechanisms of drug transport, studying aerosol deposition, controlled release studies and identification of possible drug–drug interactions. The main findings of various studies, as well as the predictive potential of this model, are presented and discussed in this review. Expert opinion: There is still a lack of mechanistic knowledge regarding transport of inhaled therapeutics across the lungs. Cell culture models such as Calu-3 provide a simple and reproducible system to study the underlying mechanisms by which inhaled therapeutics interact with the lungs. However, more complex systems that integrate particle deposition onto different cell culture systems may be useful in addressing some fundamental questions to generate a better understanding of determinants that influences pulmonary drug dissolution, absorption, metabolism and efficacy. Ultimately the use of the Calu-3 cell line provides a basic research tool that enables the development of safer and more effective inhaled therapeutics.