{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T18:06:58Z","timestamp":1784830018234,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Pulmonary drug delivery represents a promising approach for the potential localised treatment of respiratory of non-small-cell lung cancer (NSCLC). However, the efficient delivery of poorly water-soluble drugs remains challenging due to limited solubility and inadequate aerodynamic performance. This study aimed to develop and characterise inhalable dry powder formulations of zinc diethyldithiocarbamate (Zn(DDC)2) complexes with hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) and sulfobutylether-\u03b2-cyclodextrin (SBE-\u03b2-CD) for potential pulmonary administration. Methods: Formulations were prepared by freeze-drying and spray-drying, with leucine incorporated at 0%, 5%, and 10% w\/w. Formulations were prepared via freeze-drying and spray-drying with leucine incorporation (0%, 5% and 10% w\/w) to evaluate their physicochemical properties, flowability and aerodynamic performance. Results: Spray-dried formulations exhibited significantly lower densities (as low as 1.03 \u00b1 0.71 g\/cm3), enhanced flowability, improved aerosolisation and higher fine particle fraction (FPF) values (up to 40.12 \u00b1 0.60%) compared to freeze-dried powders (20.03 \u00b1 2.79%). The incorporation of leucine further reduced powder density down to 0.72 \u00b1 0.34 g\/cm3 and increased surface corrugation as shown in SEM images, improving aerosolisation performance, with FPF values up to 76.77 \u00b1 1.18%. Next Generation Impactor (NGI) analysis confirmed that leucine-containing formulations exhibited a greater proportion of particles within the respirable aerodynamic diameter range (1\u20135 \u03bcm), suggesting suitability for deep lung deposition. Conclusions: These results demonstrate that spray-dried Zn(DDC)2\u2013cyclodextrin powders, particularly those modified with 10% leucine, offer excellent potential for pulmonary delivery in NSCLC therapy. Further in vivo studies are warranted to evaluate therapeutic efficacy and safety.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080904","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and Development of Dry Powder Cyclodextrin Complexes of Zinc Diethyldithiocarbamate for Pulmonary Drug Delivery"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6535-8236","authenticated-orcid":false,"given":"Ay\u015fe","family":"Kaya","sequence":"first","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Medicine and Social Care, Centre for Biomedicine and Health Innovation, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basel","family":"Arafat","sequence":"additional","affiliation":[{"name":"Jordan Center for Pharmaceutical Science, Amman 11195, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-7583","authenticated-orcid":false,"given":"Havovi","family":"Chichger","sequence":"additional","affiliation":[{"name":"Biomedical Research Group, School of Life Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8661-6353","authenticated-orcid":false,"given":"Barbara","family":"Pierscionek","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Medicine and Social Care, Centre for Biomedicine and Health Innovation, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-2859","authenticated-orcid":false,"given":"Mohammad","family":"Najlah","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Medicine and Social Care, Centre for Biomedicine and Health Innovation, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organisation (2015, July 24). 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