{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:02:23Z","timestamp":1789707743657,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["P20GM103648"],"award-info":[{"award-number":["P20GM103648"]}]},{"award":["P20GM103648"],"award-info":[{"award-number":["P20GM103648"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Current treatments for tuberculosis (TB) are complex and associated with severe side effects; thus, drugs with minimal side effects would be desirable as additions to current therapies to combat the global TB epidemic. OHet72 is a novel compound with in vitro activity against Mycobacterium tuberculosis but has poor water solubility. As a first step in assessing its potential for TB treatment, the goal of this study was to formulate OHet72 in a powder form that will increase its solubility compared to the unprocessed drug, and when aerosolized, ensure that most of the inhaled dose would be deposited in the alveoli. Methods: OHet72 was first formulated into nanocrystals (NCs) and then spray-dried to obtain nanostructured microparticles (nsMPs). The resulting formulations were characterized in vitro, and their rate of dissolution was assessed. Results: OHet72 NCs were oblong-shaped with an average width of 145 nm and a length of 255 nm, whereas the resulting nsMPs were spherical, with a geometric diameter of 0.64 \u03bcm and a GSD of 1.54. When aerosolized with the Pari LC\u00ae Star nebulizer, a suspension of OHet72 NCs in saline had a mass median aerodynamic diameter (MMAD) of 3.15 \u00b1 0.43 \u03bcm and a fine particle fraction (FPF, indicating the fraction that will likely be deposited in the alveoli) of 54.63 \u00b1 5.83%. In contrast, OHet72 nsMPs dispersed from the Plastiape RS01 dry powder inhaler (DPI) had a MMAD of 3.80 \u00b1 0.49 \u03bcm and an FPF of 37.16 \u00b1 6.67%. The dissolution rate of OHet72 NCs was faster (34.65 \u00b1 5.43%) than that of the unprocessed drug (0.72 \u00b1 0.34%), but the OHet72 in the nsMPs dissolved significantly faster and to a greater extent (57.55 \u00b1 5.60%) than both the unprocessed drug and the NCs. Conclusions: Based on their MMAD, GSD and FPF, OHet72 NC and nsMPs appear suitable for effective pulmonary delivery, and based on their apparent solubility and dissolution testing, they would dissolve in the lung environment.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091164","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:58:59Z","timestamp":1789545539000},"page":"1164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering of OHet72 Nanocrystals into Nanostructured Microparticles for Pulmonary Delivery of a Novel Antitubercular Drug Candidate"],"prefix":"10.3390","volume":"18","author":[{"given":"Margaret D.","family":"Bourlon","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, OK 73117, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Beathard","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, OK 73117, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6605-953X","authenticated-orcid":false,"given":"Lucila","family":"Garcia-Contreras","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, OK 73117, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023). 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