{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:53:09Z","timestamp":1785851589410,"version":"3.56.0"},"reference-count":31,"publisher":"American Chemical Society (ACS)","issue":"30","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001501","name":"University Grants Commission","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aromatase, an enzyme that facilitates the last stage in estrogen synthesis (estrogen is identified for a significant impact in the development of breast cancer), has been recognized as a potential target for therapeutic advancements for cancer. Although clinically approved aromatase inhibitors are the cornerstones of estrogen receptor-positive (ER+) breast cancer, their use is often accompanied by adverse side effects and pharmacokinetic limitations, which lead to patient compliance issues and limit therapeutic outcomes. In previous studies, compound 1(a) was identified for its superior inhibition of aromatase with an IC50 value of 54.0 nM and appreciable tumor growth inhibitory activities. Here, we demonstrated the pharmaceutical capability of 1(a) while evaluating its various features, including acute toxicity, bioavailability by developing a nanodrug delivery system, and therapeutic efficacy. In vivo acute toxicity studies confirmed the safety of compound 1(a), with no significant alterations observed. To improve the aqueous solubility and pharmacokinetic profile, a mixed micelle-based delivery system by using Pluronics P123 and F127 was developed, and a 2:1 formulation was optimized for demonstrating excellent drug loading (8.8%) and entrapment efficiency (80%). The micellar formulation significantly enhanced the solubility, stability, % growth inhibition, and cellular uptake of 1(a) against MCF-7 and MDA-MB-231 cell lines and intestine permeability. An in vitro drug release study performed at pH 1.2, 6.8, and 7.4 indicated the sustained release behavior of 1(a). Overall, the results of these experiments supported the potential of Pluronics as a drug delivery system for the potent aromatase inhibitor.<\/jats:p>","DOI":"10.1021\/acsomega.6c01669","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:42:30Z","timestamp":1784562150000},"page":"44812-44825","source":"Crossref","is-referenced-by-count":0,"title":["Developing Mixed\nMicelle Delivery Systems for Aromatase\nInhibitors"],"prefix":"10.1021","volume":"11","author":[{"given":"Sheetal","family":"Vermani","sequence":"first","affiliation":[{"name":"Guru Nanak Dev University , , ,","place":["Amritsar, India, 143005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2332-5257","authenticated-orcid":true,"given":"Palwinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Guru Nanak Dev University , , ,","place":["Amritsar, India, 143005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Guru Nanak Dev University , , ,","place":["Amritsar, India, 143005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neena","family":"Bedi","sequence":"additional","affiliation":[{"name":"Guru Nanak Dev University , , ,","place":["Amritsar, India, 143005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sombir","family":"Jaglan","sequence":"additional","affiliation":[{"name":"Guru Nanak Dev University , , ,","place":["Amritsar, India, 143005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satwinderjeet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Guru Nanak Dev University , , ,","place":["Amritsar, India, 143005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheikh Showkat","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Guru Nanak Dev University , , ,","place":["Amritsar, India, 143005"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"issue":"10","key":"2026080409263717600_cit1","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1177\/1933719108322441","article-title":"Novel Promoter I.8\nand Promoter Usage in the CYP19 (Aromatase) Gene","volume":"15","author":"Demura","year":"2008","journal-title":"Reprod. Sci."},{"key":"2026080409263717600_cit2","doi-asserted-by":"publisher","first-page":"493","DOI":"10.2147\/ijwh.s69907","article-title":"Clinical Utilities\nof Aromatase Inhibitors in Breast Cancer","volume":"7","author":"Chumsri","year":"2015","journal-title":"Int.\nJ. Women\u2019s Health."},{"issue":"35","key":"2026080409263717600_cit3","doi-asserted-by":"publisher","first-page":"46090","DOI":"10.1021\/acsami.4c09901","article-title":"Acid-Resistant Nano-Antioxidants\nBased on Epigallocatechin Gallate Alleviate Acute Intestinal and Kidney\nInflammation","volume":"16","author":"Pan","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026080409263717600_cit4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.22203\/eCM.v053a01","article-title":"Matrine Nanoparticles Improve Functional\nConstipation and Associated Depressive Behavioral Disorders by Modulating\nthe Gut-Brain Axis","volume":"53","author":"Liu","year":"2025","journal-title":"Eur. Cells Mater."},{"key":"2026080409263717600_cit5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2022.103655","article-title":"A Comprehensive Review\non Novel Delivery Approaches for Exemestane","volume":"75","author":"Chaturvedi","year":"2022","journal-title":"J. Drug Delivery Sci. Technol."},{"issue":"8","key":"2026080409263717600_cit6","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/s1470-2045(06)70767-7","article-title":"Comprehensive Side-Effect Profile of Anastrozole and Tamoxifen as\nAdjuvant Treatment for Early-Stage Breast Cancer: Long-Term Safety\nAnalysis of the ATAC Trial","volume":"7","year":"2006","journal-title":"Lancet Oncol."},{"issue":"5","key":"2026080409263717600_cit7","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1093\/omcr\/omaf062","article-title":"Anastrozole-induced\nautoimmune hepatitis: a rare case report and literature review","volume":"2025","author":"Haghollahi","year":"2025","journal-title":"Oxf Med. Case Reports."},{"key":"2026080409263717600_cit8","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121074","article-title":"Letrozole: Pharmacology, Toxicity and Potential Therapeutic\nEffects","volume":"310","author":"Mukherjee","year":"2022","journal-title":"Life Sci."},{"key":"2026080409263717600_cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.123136","article-title":"Polymer-Lipid\nHybrid Nanoparticles\nof Exemestane for Improved Oral Bioavailability and Anti-Tumor Efficacy:\nAn Extensive Preclinical Investigation","volume":"642","author":"Rizwanullah","year":"2023","journal-title":"Int.\nJ. Pharm."},{"issue":"7","key":"2026080409263717600_cit10","doi-asserted-by":"publisher","DOI":"10.1002\/pat.70235","article-title":"Preparation and Characterization\nof Anastrozole Nanocrystal Fast Dissolving Tablets Using Super Disintegrants\nand Co-Processed Excipients for Enhanced Drug Release","volume":"36","author":"Akbar","year":"2025","journal-title":"Polym. Adv. Technol."},{"key":"2026080409263717600_cit11","doi-asserted-by":"publisher","first-page":"6233","DOI":"10.2147\/IJN.S384085","article-title":"In Vitro Development\nof Controlled-Release Nanoniosomes for Improved Delivery and Anticancer\nActivity of Letrozole for Breast Cancer Treatment","volume":"17","author":"Ahmadi","year":"2022","journal-title":"Int. J. Nanomedicine"},{"issue":"4","key":"2026080409263717600_cit12","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1080\/10837450.2019.1703739","article-title":"Folic Acid Receptor-Targeted Solid\nLipid Nanoparticles to Enhance Cytotoxicity of Letrozole through Induction\nof Caspase-3 Dependent-Apoptosis for Breast Cancer Treatment","volume":"25","author":"Yassemi","year":"2020","journal-title":"Pharm. Dev. Technol."},{"key":"2026080409263717600_cit13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.116111","article-title":"Targeting Aromatase\nto Restrain Oestrogen Production and Developing Efficacious Interventions\nagainst ER-Positive Cancer","volume":"265","author":"Rani","year":"2024","journal-title":"Eur. J. Med. Chem."},{"issue":"1","key":"2026080409263717600_cit14","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/S0065-2571(00)00013-3","article-title":"The Enhanced\nPermeability and Retention (EPR) Effect in Tumor Vasculature: The\nKey Role of Tumor-Selective Macromolecular Drug Targeting","volume":"41","author":"Maeda","year":"2001","journal-title":"Adv. Enzyme Regul."},{"key":"2026080409263717600_cit15","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ejpb.2016.12.019","article-title":"Polymeric\nMixed Micelles as Nanomedicines: Achievements and Perspectives","volume":"113","author":"Cagel","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"issue":"5","key":"2026080409263717600_cit16","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1007\/s10637-010-9399-1","article-title":"A Phase 2 Study of SP1049C, Doxorubicin in P-Glycoprotein-Targeting\nPluronics, in Patients with Advanced Adenocarcinoma of the Esophagus\nand Gastroesophageal Junction","volume":"29","author":"Valle","year":"2011","journal-title":"Invest. New Drugs"},{"issue":"15","key":"2026080409263717600_cit17","doi-asserted-by":"publisher","DOI":"10.3390\/polym14153007","article-title":"Drug Delivery\nSystems Based on Pluronic Micelles with Antimicrobial Activity","volume":"14","author":"Popovici","year":"2022","journal-title":"Polymers"},{"issue":"1","key":"2026080409263717600_cit18","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.colsurfb.2009.03.028","article-title":"Effect of Polymer Viscosity on Physicochemical Properties\nand Ocular Tolerance of FB-Loaded PLGA Nanospheres","volume":"72","author":"Arau\u0301jo","year":"2009","journal-title":"Colloids Surf., B"},{"key":"2026080409263717600_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2024.124799","article-title":"Effects of Nanoparticle\nSize, Shape, and Zeta Potential on Drug Delivery","volume":"666","author":"O\u0308ztu\u0308rk","year":"2024","journal-title":"Int. J. Pharm."},{"issue":"12","key":"2026080409263717600_cit20","doi-asserted-by":"publisher","first-page":"5572","DOI":"10.1039\/D0NA00582G","article-title":"Using Pyrene\nto Probe the Effects\nof Poloxamer Stabilisers on Internal Lipid Microenvironments in Solid\nLipid Nanoparticles","volume":"2","author":"Taylor","year":"2020","journal-title":"Nanoscale Adv."},{"issue":"1","key":"2026080409263717600_cit21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/0378-5173(83)90064-9","article-title":"Mechanisms\nof Solute Release from Porous Hydrophilic Polymers","volume":"15","author":"Korsmeyer","year":"1983","journal-title":"Int. J. Pharm."},{"key":"2026080409263717600_cit22","doi-asserted-by":"publisher","DOI":"10.1038\/srep31417","article-title":"The Use of\nDAPI Fluorescence Lifetime Imaging for Investigating Chromatin Condensation\nin Human Chromosomes","volume":"6","author":"Estandarte","year":"2016","journal-title":"Sci. Rep."},{"issue":"7","key":"2026080409263717600_cit23","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1007\/s10439-007-9265-2","article-title":"Mitochondrial\nInner Membrane Electrophysiology Assessed by Rhodamine-123 Transport\nand Fluorescence","volume":"35","author":"Huang","year":"2007","journal-title":"Ann. Biomed. Eng."},{"issue":"1","key":"2026080409263717600_cit24","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-022-02211-1","article-title":"Non-Ionic Surfactants\nas a P-Glycoprotein (P-gp) Efflux Inhibitor for Optimal Drug Delivery\u2500A\nConcise Outlook","volume":"23","author":"Rathod","year":"2022","journal-title":"AAPS PharmSciTech"},{"key":"2026080409263717600_cit25","article-title":"Acute Oral Toxicity\u2500Acute\nToxic Class Method","volume-title":"OECD Guideline for\nTesting of Chemicals, Guideline 423","author":"OECD.","year":"2001"},{"issue":"18","key":"2026080409263717600_cit26","doi-asserted-by":"publisher","first-page":"6194","DOI":"10.1021\/jp8093879","article-title":"Association of a Hydrophobically Modified Polyelectrolyte and a Block\nCopolymer Followed by Fluorescence Techniques","volume":"113","author":"Costa","year":"2009","journal-title":"J. Phys. Chem. B"},{"issue":"5","key":"2026080409263717600_cit27","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1007\/s13346-023-01470-0","article-title":"Preparation, Characterization, Pharmacokinetics\nand Ulcerative Colitis Treatment of Hyperoside-Loaded Mixed Micelles","volume":"14","author":"Jin","year":"2024","journal-title":"Drug Delivery Transl. Res."},{"issue":"1\u20132","key":"2026080409263717600_cit28","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.ijpharm.2005.03.022","article-title":"Development and Application\nof High Throughput Plasma Stability Assay for Drug Discovery","volume":"297","author":"Di","year":"2005","journal-title":"Int. J. Pharm."},{"issue":"6","key":"2026080409263717600_cit29","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1007\/s12010-009-8689-6","article-title":"Role of Human\nLiver Microsomes in in Vitro Metabolism\nof Drugs\u2500A Review","volume":"160","author":"Asha","year":"2010","journal-title":"Appl. Biochem. Biotechnol."},{"key":"2026080409263717600_cit30","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/978-1-4939-2074-7_26","article-title":"General Cytotoxicity\nAssessment by Means of the MTT Assay","volume":"1250","author":"Tolosa","year":"2015","journal-title":"Methods\nMol. Biol."},{"issue":"1","key":"2026080409263717600_cit31","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0165-0270(98)00147-2","article-title":"Annexin V\nBinding Assay as a Tool to Measure Apoptosis in Differentiated Neuronal\nCells","volume":"86","author":"Schutte","year":"1998","journal-title":"J. Neurosci. Methods"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c01669","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/30\/44812\/66060664\/acsomega.6c01669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/30\/44812\/66060664\/acsomega.6c01669.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:26:44Z","timestamp":1785850004000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/30\/44812\/5221325\/Developing-Mixed-Micelle-Delivery-Systems-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":31,"journal-issue":{"issue":"30","published-online":{"date-parts":[[2026,7,20]]},"published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c01669","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}