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Recent Trends in Preclinical Models for Inhalation and Nasal Drug Delivery

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 12994

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Special Issue Editors

Dr. Laurent Vecellio

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Guest Editor

Research Centre for Respiratory Diseases, University of Tours, 37000 Tours, France
Interests: in vitro, animal, and clinical studies for inhalation; nebulizers; lung and nasal delivery; inhaled bacteriophages, peptides and antibodies; nasal spray; nose to brain delivery

Dr. Frédéric Ducancel

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Guest Editor

Centre de Recherche de Fontenay-aux-Roses, CEA, 18 Route du Panorama, 92260 Fontenay-aux-Roses, France
Interests: infectious diseases; animal experimentation; preclinical models; aerosol

Special Issue Information

Dear Colleagues,

Inhalation and nasal drug delivery are widely used to treat airway diseases, but they are also in development to target other organs like heart via the lung or brain via the nose. Different preclinical models are used to evaluate this way of administration, but they have limitations. The aerosol research is a complex topic including different scientific knowledge and expertise, like mathematics, physics, biology, pharmacology and animals. Standard and regulatory preclinical models generally provide partial information and could be questionable in terms of clinical relevance. Recent advances in aerosol knowledge, emerging technologies like 3D print, microfluidic, imaging or IA may improve the quality of models and should help models to give larger information. This Special issue shall cover recent trends in preclinical models for inhalation and nasal drug delivery.

Dr. Laurent Vecellio
Dr. Frédéric Ducancel
Guest Editor

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Keywords

nebulizer
mist
inhalation
nasal drug delivery
electronic devices
aerosols
medical device

Published Papers (4 papers)

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Research

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12 pages, 683 KiB

Open AccessArticle

The Impact of Head Model Choice on the In Vitro Evaluation of Aerosol Drug Delivery

by Lauren Gallagher, Mary Joyce, Barry Murphy, Marc Mac Giolla Eain and Ronan MacLoughlin

Pharmaceutics 2022, 14(1), 24; https://doi.org/10.3390/pharmaceutics14010024 - 23 Dec 2021

Cited by 8 | Viewed by 2635

Abstract

There are variations in the values reported for aerosol drug delivery across in vitro experiments throughout the published literature, and often with the same devices or similar experimental setups. Factors contributing to this variability include, but are not limited to device type, equipment settings, drug type and quantification methods. This study assessed the impact of head model choice on aerosol drug delivery using six different adults and three different paediatric head models in combination with a facemask, mouthpiece, and high-flow nasal cannula. Under controlled test conditions, the quantity of drug collected varied depending on the choice of head model. Head models vary depending on a combination of structural design differences, facial features (size and structure), internal volume measurements and airway geometries and these variations result in the differences in aerosol delivery. Of the widely available head models used in this study, only three were seen to closely predict in vivo aerosol delivery performance in adults compared with published scintigraphy data. Further, this testing identified the limited utility of some head models under certain test conditions, for example, the range reported across head models was aerosol drug delivery of 2.62 ± 2.86% to 37.79 ± 1.55% when used with a facemask. For the first time, this study highlights the impact of head model choice on reported aerosol drug delivery within a laboratory setting and contributes to explaining the differences in values reported within the literature. Full article

(This article belongs to the Special Issue Recent Trends in Preclinical Models for Inhalation and Nasal Drug Delivery)

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19 pages, 3790 KiB

Open AccessArticle

Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment

by Wing-Hin Lee, Ching-Yee Loo, Daniela Traini and Paul M. Young

Pharmaceutics 2021, 13(1), 9; https://doi.org/10.3390/pharmaceutics13010009 - 22 Dec 2020

Cited by 29 | Viewed by 3279

Abstract

Despite the effort to develop efficient targeted drug delivery for lung cancer treatment, the outcome remains unsatisfactory with a survival rate of 15% after 5 years of diagnosis. Inhalation formulation is an ideal alternative that could ensure the direct deposition of chemotherapeutics to the lungs. However, the design of an inhalable formulation that could simultaneously achieve a high local chemotherapeutic dose to the solid tumor and exert low pulmonary toxicities is a challenge, as the presence of 10–30% of chemotherapeutics in the lung is sufficient to induce toxicity. Therefore, this study aimed to develop a simple dry powder inhalation (DPI) formulation containing a model chemotherapeutic agent (paclitaxel, PTX) and a natural antioxidant (curcumin, CUR) that acts to protect healthy lung cells from injury during direct lung delivery. The co-jet-milling of CUR and PTX resulted in formulations with suitable aerosol performance, as indicated in the high fine particle fractions (FPF) (>60%) and adequate mass median aerodynamic diameter (MMAD). The CUR/PTX combination showed a more potent cytotoxic effect against lung cancer cells. This is evident from the induction of apoptosis/necrotic cell death and G2/M cell cycle arrests in both A549 and Calu-3 cells. The increased intracellular ROS, mitochondrial depolarization and reduced ATP content in A549 and Calu-3 cells indicated that the actions of CUR and PTX were associated with mitochondrial oxidative stress. Interestingly, the presence of CUR is crucial to neutralize the cytotoxic effects of PTX against healthy cells (Beas-2B), and this is dose-dependent. This study presents a simple approach to formulating an effective DPI formulation with preferential cytotoxicity towards lung cancer. Full article

(This article belongs to the Special Issue Recent Trends in Preclinical Models for Inhalation and Nasal Drug Delivery)

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15 pages, 2460 KiB

Open AccessArticle

A Compartment-Based Mathematical Model for Studying Convective Aerosol Transport in Newborns Receiving Nebulized Drugs during Noninvasive Respiratory Support

by Francesco Tarantini, Ilaria Milesi, Xabier Murgia, Federico Bianco and Raffaele L. Dellacà

Pharmaceutics 2020, 12(10), 936; https://doi.org/10.3390/pharmaceutics12100936 - 30 Sep 2020

Cited by 2 | Viewed by 1791

Abstract

Nebulization could be a valuable solution to administer drugs to neonates receiving noninvasive respiratory support. Small and irregular tidal volumes and air leaks at the patient interface, which are specific characteristics of this patient population and are primarily responsible for the low doses delivered to the lung (D_DL) found in this application, have not been thoroughly addressed in in vitro and in vivo studies for quantifying D_DL. Therefore, we propose a compartment-based mathematical model able to describe convective aerosol transport mechanisms to complement the existing deposition models. Our model encompasses a mechanical ventilator, a nebulizer, and the patient; the model considers the gas flowing between compartments, including air leaks at the patient–ventilator interface. Aerosol particles are suspended in the gas flow and homogeneously distributed. The impact of breathing pattern variability, volume of the nebulizer, and leaks level on D_DL is assessed in representative conditions. The main finding of this study is that convective mechanisms associated to air leaks and breathing patterns with tidal volumes smaller than the nebulizer dramatically reduce the D_DL (up to 70%). This study provides a possible explanation to the inconsistent results of drug aerosolization in clinical studies and may provide guidance to improve nebulizer design and clinical procedures. Full article

(This article belongs to the Special Issue Recent Trends in Preclinical Models for Inhalation and Nasal Drug Delivery)

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Review

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12 pages, 3608 KiB

Open AccessReview

In Vitro Anatomical Models for Nasal Drug Delivery

by Gerallt Williams and Julie D. Suman

Pharmaceutics 2022, 14(7), 1353; https://doi.org/10.3390/pharmaceutics14071353 - 26 Jun 2022

Cited by 16 | Viewed by 4612

Abstract

Nasal drug delivery has been utilized for locally acting diseases for decades. The nose is also a portal to the systemic circulation and central nervous system (CNS). In the age of SARS-CoV2, the development of nasal sprays for vaccination and prophylaxis of respiratory diseases is increasing. As the number of nasal drug delivery applications continue to grow, the role of targeted regional deposition in the nose has become a factor is nasal drug development. In vitro tools such as nasal casts help facilitate formulation and product development. Nasal deposition has been shown to be linked to pharmacokinetic outcomes. Developing an understanding of the complex nasal anatomy and intersubject variability can lead to a better understanding of where the drug will deposit. Nasal casts, which are replicas of the human nasal cavity, have evolved from models made from cadavers to complex 3D printed replicas. They can be segmented into regions of interest for quantification of deposition and different techniques have been utilized to quantify deposition. Incorporating a nasal cast program into development can help differentiate formulations or physical forms such as nasal powder versus a liquid. Nasal casts can also help develop instructions for patient use to ensure deposition in the target deposition site. However, regardless of the technique used, this in vitro tool should be validated to ensure the results reflect the in vivo situation. In silico, CFD simulation or other new developments may in future, with suitable validation, present additional approaches to current modelling, although the complexity and wide degree of variability in nasal anatomy will remain a challenge. Nonetheless, nasal anatomical models will serve as effective tools for improving the understanding of nasal drug delivery. Full article

(This article belongs to the Special Issue Recent Trends in Preclinical Models for Inhalation and Nasal Drug Delivery)

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