Editorial pubs.acs.org/molecularpharmaceutics
Advances in Respiratory and Nasal Drug Delivery
T
molecule and polymeric excipients is a regulatory expectation for the conduct of clinical trials and the eventual commercialization of new pharmaceutical products. In a concise review, Wolff provides an overview of the toxicological requirements to assess the safety of drugs and excipients intended for pulmonary or nasal delivery. Given that macrophage response is a common observation in preclinical safety studies, Hoffman et al. report on their strategy to differentiate among the druginduced macrophage responses to inhaled medicines. Collectively, these efforts to characterize and understand drug delivery on the particle, cellular, and molecular levels constitute meaningful progress. Most importantly, this work supports the development of medicines that improve patients’ lives. Toward this end, Miller et al. demonstrate how particle engineering has enabled development of an approved inhaled drug product that meaningfully reduces the treatment burden to cystic fibrosis patients. Recognizing the importance of global health, Choi et al. exemplify the frontiers of respiratory and nasal drug delivery through their work on vaccination to offer protection to Ebola infection. In closing, we would like to thank the authors for their contributions to advancing our understanding of the field. Many thanks to our coordinating editor, Ms. Kim Barrett, for her assistance in completing this issue; and to Prof. Gordon Amidon many thanks as well for encouraging us to pursue the creation of the present special issue. We hope that you enjoy these articles and find them to be insightful, thought-provoking, and perhaps a valuable springboard for your own research.
his special issue brings together a rich variety of studies that cover key aspects of respiratory and nasal drug delivery: formulation and delivery, deposition, and absorption. These investigations involve local delivery to the lung epithelium or nasal sinuses, or transport to the systemic circulation or the brain. The contributions of this issue reflect the diversity in molecular properties; drugs may be small molecules or macromolecules or vaccine vectors expressing viral antigens, hydrophilic or hydrophobic, soluble or insoluble, crystalline or amorphous. Formulation studies range from mechanistic studies on particle formation during spray drying (Baldelli et al.), to molecular approaches to enhance the action of pyrazinoic acid salts (Durham et al.), to the use of a polymer to improve transgene expression in the development of a nasal Ebola vaccine (Choi et al.). Given the serious concerns about antibiotic-resistant infections, increased attention is being paid to developing treatments for lung infections. Studies in this issue comprise a variety of rational formulation and delivery approaches for anti-infective agents. Das et al. formulate an antifungal agent using PLGA nanoparticles, demonstrating a prolonged lung residence time. Zhou et al. and Costabile et al. formulate antibiotics to treat planktonic and, more importantly, biofilm phenotoypes of Pseudomonas aeruginosa. In accordance with the “hit hard and hit fast” philosophy for treatment of lung infections, Sullivan et al. and Garcia Contreras et al. demonstrate in animal models the delivery of vancomycin and rifampicin, respectively. Here, targeting the lungs enables a significantly higher local concentration and lower systemic levels of drug, reducing off-target effects. Respiratory and nasal drug delivery can be thought of as topical delivery of aerosols to epithelia. While there is a considerable body of literature on formulation and delivery of aerosols, much less is known about what happens after a particle is deposited on an epithelium. The commonly used approach to correlate dissolution rates to oral absorption rates has now been extended to drugs administered via inhalation by studying the dissolution of inhaled corticosteroids of a respirable particle size (Rohrschneider et al.). Beyond dissolution, our understanding of the phenomena that occur on a molecular and cellular level is growing. Motivated by the number of in vivo and ex vivo studies using different animal species to understand nasal drug absorption, Al-Ghabeish et al. provide a comparative study of the expression of several drug transporters in humans and animal species. Transporters in the lungs are also investigated, where Salomon et al. assess an important class of compoundsβ2-adrenergic agonistsfor their influence on organic cation transporters. Given the role of peptides in control of metabolic and other functions, Spetter and Hallschmid review the literature on intranasal delivery of neuropeptides. Excipients, the inactive ingredients in a formulation, are critical components in the formulation of most inhaled drug products, often playing an important role in manufacturability and product performance. Assessment of the safety of small © 2015 American Chemical Society
David Lechuga-Ballesteros,* Guest Editor Pearl Therapeutics, Redwood City, California 94063, United States
Danforth P. Miller, Guest Editor
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Novartis Pharmaceuticals, San Carlos, California 94070, United States
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.
Special Issue: Advances in Respiratory and Nasal Drug Delivery Published: August 3, 2015 2561
DOI: 10.1021/acs.molpharmaceut.5b00495 Mol. Pharmaceutics 2015, 12, 2561−2561
