Special Issue "Respiratory and Nasal Drug Delivery"

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A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (20 December 2013)

Special Issue Editor

Guest Editor
Dr. Remigius U. Agu

Biopharmaceutics and Drug Delivery Laboratory, Dalhousie University, Halifax NS, Canada
Website | E-Mail
Interests: respiratory/nasal; transporters; toxicity screening; drug delivery

Special Issue Information

Dear Colleagues,

Novel developments in the fields of Biotechnology and Combinatorial Chemistry rekindled overall interest in exploring the respiratory and nasal routes for systemic delivery of biomolecules (e.g., proteins, peptides and nucleic acids). Pursuits in these areas of drug delivery are not limited to macromolecules and systemic delivery. Many research groups are consistently looking for more effective ways to deliver small molecules local to the lung, nasal sinuses and brain via the nasal route. Novel approaches for efficient systemic and local drug delivery have been developed over the past few years. Such strategies include novel formulations (micro/nano particles, stent) and delivery devices. Successful respiratory and nasal drug delivery also requires sound experimental methods/model development. This special issue entitled: "Respiratory and Nasal Drug Delivery" will deal with key aspects of modern respiratory and nasal delivery. Micro-/nano-particulate delivery; formulation/delivery of aerosols and dry powders; optimization of nasal and respiratory drug absorption using in vitro, ex vivo and in situ tissue culture and animal models; brain targeting via the nasal route; exploration of mechanisms of epithelial drug permeation (e.g., active transport mechanisms); aerosol delivery simulation and other particle projectile studies; toxicological aspects of nasal and respiratory drug delivery, especially micro and nanoparticles; pharmacodynamics and pharmacokinetics of novel formulations following nasal and inhalational administration will be covered. Other relevant topics including muco-/bio-adhesive delivery, cilio-toxicity screening, delivery devices development, optimization and validation are also welcomed.

Dr. Remigius U. Agu
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • respiratory
  • nasal
  • pulmonary
  • drug delivery
  • devices
  • aerosol
  • drug targeting

Published Papers (7 papers)

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Research

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Open AccessArticle Preliminary Studies on Validation of Calu-3 Cell Line as a Model for Screening Respiratory Mucosa Irritation and Toxicity
Pharmaceutics 2014, 6(2), 268-280; doi:10.3390/pharmaceutics6020268
Received: 26 January 2014 / Revised: 29 May 2014 / Accepted: 3 June 2014 / Published: 13 June 2014
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Abstract
There is need to develop reproducible methods and experimental models for screening mucosal irritation and toxicity for drugs and pharmaceutical excipients. The aim of this study was to validate Calu-3 cell line as a model for screening respiratory irritation and toxicity of drugs
[...] Read more.
There is need to develop reproducible methods and experimental models for screening mucosal irritation and toxicity for drugs and pharmaceutical excipients. The aim of this study was to validate Calu-3 cell line as a model for screening respiratory irritation and toxicity of drugs and excipients. Eighteen test compounds were selected according to their irritation potential and European Centre for the Validation of Alternative Methods (ECVAM) guidelines. Cell toxicity and irritation was determined using MTT assay. Data analysis and interpretation were done using modified ECVAM approach; where replicate values met acceptance criteria if percent relative standard deviation (RSD) of the raw data is <18%. Compounds with mean relative viability values of 50% and below were classified as irritant (I); those above 50% were non-irritant (NI). At low concentration (0.2% w/v) and 1 h incubation, the Calu-3 cell culture model accurately predicted the toxicity of most test compounds. The specificity of our proposed model (percentage of in vivo non-irritants correctly predicted), concordance (percentage of compounds correctly predicted) and sensitivity (percentage of in vivo irritants correctly predicted) at 0.2% w/v and 60 min exposure were 100%, 72%, and 44%, respectively. In conclusion, the Calu-3 cell line in conjunction with MTT assay appears to be a potentially useful tool for screening drugs and excipients for respiratory mucosa irritation and toxicity. However, as the data reported in this study were solely based on MTT assay, additional studies are needed using other toxicity-/irritation-indicating methods to confirm the observed trend. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessArticle Performance of Dry Powder Inhalers with Single Dosed Capsules in Preschool Children and Adults Using Improved Upper Airway Models
Pharmaceutics 2014, 6(1), 36-51; doi:10.3390/pharmaceutics6010036
Received: 20 December 2013 / Revised: 20 January 2014 / Accepted: 23 January 2014 / Published: 6 February 2014
Cited by 4 | PDF Full-text (366 KB) | HTML Full-text | XML Full-text
Abstract
The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction
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The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction port according to the European Pharmacopeia were used for in vitro testing of dry powder inhalers with single dosed capsules (Cyclohaler®, Handihaler® and Spinhaler®). Deposition measurements were performed using steady flow rates of 30 and 60 L/min for the Handihaler®/Spinhaler® and 30, 60 and 75 L/min for the Cyclohaler®. The inhalation volume was set at 1 L. For the Cyclohaler®, the in vitro testing was supplemented by a pediatric inhalation profile. Slight differences of pulmonary deposition between the idealized adult (11%–15%) and pediatric (9%–11%) upper airway model were observed for the Cyclohaler®. The applied pediatric inhalation profile resulted in a reduction of pulmonary deposition by 5% compared to steady conditions and indicated the influence of the inhalation pattern on the amount of pulmonary deposited particles. The comparison of two pediatric upper airway models showed no differences. The performance of the Handihaler® was similar to the Cyclohaler®. The Spinhaler® showed an insufficient performance and limited reproducibility in our investigations. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessArticle Electrostatic Charge Effects on Pharmaceutical Aerosol Deposition in Human Nasal–Laryngeal Airways
Pharmaceutics 2014, 6(1), 26-35; doi:10.3390/pharmaceutics6010026
Received: 13 September 2013 / Revised: 23 January 2014 / Accepted: 26 January 2014 / Published: 29 January 2014
Cited by 11 | PDF Full-text (1346 KB) | HTML Full-text | XML Full-text
Abstract
Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the
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Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the upper airways, where particles come in close proximity to the narrow turbinate surface, and before charge dissipation occurs as a result of high humidity. The objective of this study was to quantitatively evaluate the deposition of charged aerosols in an MRI-based nasal–laryngeal airway model. Particle sizes of 5 nm–30 µm and charge levels ranging from neutralized to ten times the saturation limit were considered. A well-validated low Reynolds number (LRN) k–ω turbulence model and a discrete Lagrangian tracking approach that accounted for electrostatic image force were employed to simulate the nasal airflow and aerosol dynamics. For ultrafine aerosols, electrostatic charge was observed to exert a discernible but insignificant effect. In contrast, remarkably enhanced depositions were observed for micrometer particles with charge, which could be one order of magnitude larger than no-charge depositions. The deposition hot spots shifted towards the anterior part of the upper airway as the charge level increased. Results of this study have important implications for evaluating nasal drug delivery devices and for assessing doses received from pollutants, which often carry a certain level of electric charges. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Review

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Open AccessReview Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives
Pharmaceutics 2014, 6(3), 378-415; doi:10.3390/pharmaceutics6030378
Received: 18 February 2014 / Revised: 20 June 2014 / Accepted: 24 June 2014 / Published: 10 July 2014
Cited by 4 | PDF Full-text (1638 KB) | HTML Full-text | XML Full-text
Abstract
Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid
[...] Read more.
Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessReview Drug-Eluting Nasal Implants: Formulation, Characterization, Clinical Applications and Challenges
Pharmaceutics 2014, 6(2), 249-267; doi:10.3390/pharmaceutics6020249
Received: 26 January 2014 / Revised: 28 March 2014 / Accepted: 7 May 2014 / Published: 27 May 2014
Cited by 3 | PDF Full-text (582 KB) | HTML Full-text | XML Full-text
Abstract
Chronic inflammation and infection of the nasal sinuses, also referred to as Chronic Rhinosinusitis (CRS), severely affects patients’ quality of life. Adhesions, ostial stenosis, infection and inflammation relapses complicate chronic sinusitis treatment strategies. Drug-eluting stents, packings or implants have been suggested as reasonable
[...] Read more.
Chronic inflammation and infection of the nasal sinuses, also referred to as Chronic Rhinosinusitis (CRS), severely affects patients’ quality of life. Adhesions, ostial stenosis, infection and inflammation relapses complicate chronic sinusitis treatment strategies. Drug-eluting stents, packings or implants have been suggested as reasonable alternatives for addressing these concerns. This article reviewed potential drug candidates for nasal implants, formulation methods/optimization and characterization methods. Clinical applications and important considerations were also addressed. Clinically-approved implants (Propel™ implant, the Relieva stratus™ MicroFlow spacer, and the Sinu-Foam™ spacer) for CRS treatment was an important focus. The advantages and limitations, as well as future considerations, challenges and the need for additional research in the field of nasal drug implant development, were discussed. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessReview Analytical Challenges and Regulatory Requirements for Nasal Drug Products in Europe and the U.S.
Pharmaceutics 2014, 6(2), 195-219; doi:10.3390/pharmaceutics6020195
Received: 20 December 2013 / Revised: 24 March 2014 / Accepted: 31 March 2014 / Published: 11 April 2014
Cited by 3 | PDF Full-text (5473 KB) | HTML Full-text | XML Full-text
Abstract
Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization
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Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Other

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Open AccessConcept Paper An Evaluation of Intranasal Sufentanil and Dexmedetomidine for Pediatric Dental Sedation
Pharmaceutics 2014, 6(1), 175-184; doi:10.3390/pharmaceutics6010175
Received: 5 November 2013 / Revised: 22 January 2014 / Accepted: 13 February 2014 / Published: 21 March 2014
Cited by 6 | PDF Full-text (245 KB) | HTML Full-text | XML Full-text
Abstract
Conscious or moderate sedation is routinely used to facilitate the dental care of the pre- or un-cooperative child. Dexmedetomidine (DEX) has little respiratory depressant effect, possibly making it a safer option when used as an adjunct to either opioids or benzodiazepines. Unlike intranasal
[...] Read more.
Conscious or moderate sedation is routinely used to facilitate the dental care of the pre- or un-cooperative child. Dexmedetomidine (DEX) has little respiratory depressant effect, possibly making it a safer option when used as an adjunct to either opioids or benzodiazepines. Unlike intranasal (IN) midazolam, IN application of DEX and sufentanil (SUF) does not appear to cause much discomfort. Further, although DEX lacks respiratory depressive effects, it is an α2-agonist that can cause hypotension and bradycardia when given in high doses or during prolonged periods of administration. The aim of this feasibility study was to prospectively assess IN DEX/SUF as a potential sedation regimen for pediatric dental procedures. After IRB approval and informed consent, children (aged 3–7 years; n = 20) from our dental clinic were recruited. All patients received 2 μg/kg (max 40 μg) of IN DEX 45 min before the procedure, followed 30 min later by 1 μg/kg (max 20 μg) of IN SUF. An independent observer rated the effects of sedation using the Ohio State University Behavior Rating Scale (OSUBRS) and University of Michigan Sedation Scale (UMSS). The dentist and the parent also assessed the efficacy of sedation. Dental procedures were well tolerated and none were aborted. The mean OSUBRS procedure score was 2.1, the UMSS procedure score was 1.6, and all scores returned to baseline after the procedure. The average dentist rated quality of sedation was 7.6 across the 20 subjects. After discharge, parents reported one child with prolonged drowsiness and one child who vomited at home. The use of IN DEX supplemented with IN SUF provided both an effective and tolerable form of moderate sedation. Although onset and recovery are slower than with oral (PO) midazolam and transmucosal fentanyl, the quality of the sedation may be better with less risk of respiratory depression. Results from this preliminary study showed no major complications from IN delivery of these agents. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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