{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T20:55:36Z","timestamp":1787000136984,"version":"build-2736575974"},"reference-count":61,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Darolutamide (DA), a nonsteroidal antiandrogen, demonstrates significant potential as a targeted therapeutic agent for prostate cancer; however, its clinical application is limited due to its poor aqueous solubility and low oral bioavailability. To overcome these limitations, we developed a nanosuspension-based formulation (DA-NS) with a mean particle size (PS) of 143.36 \u00b1 5.24 nm, which, upon lyophilization, yielded nanocrystals (DA-NC) with a mean PS of 156.26 \u00b1 7.58 nm, aimed at enhancing the solubility and dissolution rate. Molecular dynamics simulations provided mechanistic insights into the stabilization and formation of DA-NS at the atomic level. In vitro studies demonstrated superior antitumor activity of DA-NC in PC3 prostate cancer cells, characterized by enhanced cellular internalization, nuclear condensation, and apoptotic morphology under fluorescence microscopy. Mechanistic investigations further validated its pro-apoptotic action via elevated reactive oxygen species generation and induction of DNA damage. Western blot analysis confirmed the molecular signature of apoptosis, showing downregulation of antiapoptotic Bcl-2 and upregulation of caspase-3. Pharmacokinetic evaluation revealed a 5.81-fold increase in Cmax and a 3.33-fold enhancement in AUC0\u201348 over pure DA, confirming a significant improvement in oral bioavailability (p &amp;lt; 0.0001). Importantly, DA-NC exhibited a favorable safety profile, underscoring its potential as a biocompatible and efficacious oral therapeutic strategy for advanced prostate cancer.<\/jats:p>","DOI":"10.1021\/acsabm.5c01473","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T06:39:35Z","timestamp":1761115175000},"page":"10112-10136","source":"Crossref","is-referenced-by-count":7,"title":["Strategic Nanosuspension\nof Darolutamide for Enhanced\nDissolution, Bioavailability, and Potentiated Prostate Cancer Treatment:\nInsights from Multiscale Computational Modeling"],"prefix":"10.1021","volume":"8","author":[{"given":"Ekta","family":"Pardhi","sequence":"first","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research , , , ,","place":["Hyderabad, Telangana, India, 500 037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Khemchandani","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research , , , ,","place":["Hyderabad, Telangana, India, 500 037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Pawar","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research , , , ,","place":["Hyderabad, Telangana, India, 500 037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Kharwar","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research , , ,","place":["Hyderabad, India, 500 037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gananadhamu","family":"Samanthula","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research , , , ,","place":["Hyderabad, Telangana, India, 500 037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5412-7547","authenticated-orcid":true,"given":"Manoj","family":"Dandekar","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research , , ,","place":["Hyderabad, India, 500 037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-8065","authenticated-orcid":true,"given":"Neelesh Kumar","family":"Mehra","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research , , , ,","place":["Hyderabad, Telangana, India, 500 037"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"issue":"2","key":"2026072914063048600_cit1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/S0928-0987(02)00251-8","article-title":"Nanosizing: A Formulation Approach\nfor Poorly-Water-Soluble Compounds","volume":"18","author":"Merisko-Liversidge","year":"2003","journal-title":"Eur. 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