{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:59:49Z","timestamp":1785477589798,"version":"3.56.0"},"reference-count":26,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["75F40120C00136"],"award-info":[{"award-number":["75F40120C00136"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A poly(lactic-co-glycolic acid) (PLGA)-based in situ-forming implant (ISFI) is a long-acting injectable composed of active ingredients, a biodegradable polymer and a biocompatible solvent. Understanding the role of PLGA end-caps is crucial for designing ISFI formulations due to their impact on drug delivery performance. In this study, using leuprolide acetate as a model drug, we characterized the ISFIs using computed tomography (CT) imaging to explore the influence of PLGA end-cap on the implant\u2019s formation and drug-release behavior. CT imaging enabled a detailed characterization of implant morphology and internal structure, providing new insights into the relationship between phase inversion, implant formation, and in vitro release performance. Acid-ended PLGA showed a higher initial burst release with 100% of the solvent released at 9 days and a faster release duration of the drug in the in vitro release profile. In contrast, ester-ended PLGA showed a more prolonged release profile, with the plateau phase not reached until approximately day 50. Morphological analysis from CT images of the in vitro implants revealed that acid-ended PLGA formed spherical implants with a dense outer layer, whereas ester-ended PLGA resulted in irregular shapes with a larger size expansion. In vivo CT imaging confirmed these trends, although implant evolution occurred more rapidly in biological environments. Overall, this research highlights the impact of PLGA end-caps on the performance of ISFI, providing a scientific basis for formulation development, evaluation, and optimization of ISFIs.<\/jats:p>","DOI":"10.1021\/cbmi.6c00001","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:05:04Z","timestamp":1771337104000},"page":"1509-1520","source":"Crossref","is-referenced-by-count":2,"title":["Computed Tomography\nImaging and Characteristics of\nIn Situ Forming Implants with Different PLGA Endcaps"],"prefix":"10.1021","volume":"4","author":[{"given":"Xinhao","family":"Lin","sequence":"first","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Zhen","sequence":"additional","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyyed Majid","family":"Eslami","sequence":"additional","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour Al","family":"Zouabi","sequence":"additional","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Elizabeth","family":"Ward","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mittal","family":"Darji","sequence":"additional","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheyda","family":"Ranjbar","sequence":"additional","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis K.","family":"Masese","sequence":"additional","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre\u0301 O\u2019Reilly","family":"Beringhs","sequence":"additional","affiliation":[{"name":"Food and Drug Administration , , , ,","place":["Silver Spring, Maryland, United States, 20903-1058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3872-1463","authenticated-orcid":true,"given":"Rajeswari M.","family":"Kasi","sequence":"additional","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangnan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Food and Drug Administration , , , ,","place":["Silver Spring, Maryland, United States, 20903-1058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Food and Drug Administration , , , ,","place":["Silver Spring, Maryland, United States, 20903-1058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Bin","sequence":"additional","affiliation":[{"name":"Food and Drug Administration , , , ,","place":["Silver Spring, Maryland, United States, 20903-1058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Food and Drug Administration , , , ,","place":["Silver Spring, Maryland, United States, 20903-1058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yuan","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-8156","authenticated-orcid":true,"given":"Xiuling","family":"Lu","sequence":"additional","affiliation":[{"name":"University of Connecticut , , , ,","place":["Storrs, Connecticut, United States, 06269"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"2026073101221254100_cit1","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jconrel.2021.06.017","article-title":"Challenges and opportunities\nin the development of complex generic long-acting injectable drug\nproducts","volume":"336","author":"O\u2019Brien","year":"2021","journal-title":"J. Controlled Release"},{"key":"2026073101221254100_cit2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.jconrel.2013.12.020","article-title":"Solvent\ninduced phase inversion-based\nin situ forming controlled release drug delivery implants","volume":"176","author":"Thakur","year":"2014","journal-title":"J. Controlled Release"},{"key":"2026073101221254100_cit3","doi-asserted-by":"publisher","first-page":"4324","DOI":"10.1038\/s41467-019-12141-5","article-title":"Ultra-long-acting tunable\nbiodegradable and removable controlled\nrelease implants for drug delivery","volume":"10","author":"Benhabbour","year":"2019","journal-title":"Nat. Commun."},{"key":"2026073101221254100_cit4","doi-asserted-by":"publisher","first-page":"113912","DOI":"10.1016\/j.addr.2021.113912","article-title":"Drug release from in situ forming\nimplants and advances\nin release testing","volume":"178","author":"Wang","year":"2021","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026073101221254100_cit5","doi-asserted-by":"publisher","first-page":"113758","DOI":"10.1016\/j.jconrel.2025.113758","article-title":"PLGA-based\nlong-acting injectable (LAI) formulations","volume":"382","author":"Park","year":"2025","journal-title":"J.\nControlled Release"},{"key":"2026073101221254100_cit6","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1080\/10837450.2021.1944207","article-title":"An overview of PLGA in-situ forming\nimplants based on solvent exchange technique: effect of formulation\ncomponents and characterization","volume":"26","author":"Ibrahim","year":"2021","journal-title":"Pharm. Dev.\nTechnol."},{"key":"2026073101221254100_cit7","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.jconrel.2013.08.024","article-title":"PLGA in situ implants\nformed by phase inversion: critical physicochemical\nparameters to modulate drug release","volume":"172","author":"Parent","year":"2013","journal-title":"J. Controlled\nRelease"},{"key":"2026073101221254100_cit8","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.jconrel.2012.04.016","article-title":"In situ forming implants\n- an attractive formulation principle for\nparenteral depot formulations","volume":"161","author":"Kempe","year":"2012","journal-title":"J. Controlled\nRelease"},{"key":"2026073101221254100_cit9","doi-asserted-by":"publisher","first-page":"120105","DOI":"10.1016\/j.ijpharm.2020.120105","article-title":"Effect of implant formation\non drug release kinetics of in situ forming\nimplants","volume":"592","author":"Suh","year":"2021","journal-title":"Int. J. Pharm."},{"key":"2026073101221254100_cit10","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.jconrel.2013.08.295","article-title":"The nature of peptide interactions with acid end-group PLGAs and\nfacile aqueous-based microencapsulation of therapeutic peptides","volume":"172","author":"Sophocleous","year":"2013","journal-title":"J. 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Controlled Release"},{"key":"2026073101221254100_cit14","doi-asserted-by":"publisher","first-page":"122032","DOI":"10.1016\/j.ijpharm.2022.122032","article-title":"Polymer source affects in vitro-in\nvivo correlation of leuprolide acetate PLGA microspheres","volume":"625","author":"Wan","year":"2022","journal-title":"Int. J. Pharm."},{"key":"2026073101221254100_cit15","doi-asserted-by":"publisher","first-page":"125080","DOI":"10.1016\/j.ijpharm.2024.125080","article-title":"Long-acting\ninjectable in situ forming implants: Impact of polymer attributes\nand API","volume":"670","author":"Wang","year":"2025","journal-title":"Int. J. Pharm."},{"key":"2026073101221254100_cit16","doi-asserted-by":"publisher","first-page":"4141","DOI":"10.1021\/acs.molpharmaceut.0c00619","article-title":"Physical-Chemical Characterization of Octreotide Encapsulated\nin\nCommercial Glucose-Star PLGA Microspheres","volume":"17","author":"Beig","year":"2020","journal-title":"Mol.\nPharmaceutics"},{"key":"2026073101221254100_cit17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpharm.2019.04.023","article-title":"Encapsulation and release\nof doxycycline from electrospray-generated\nPLGA microspheres: Effect of polymer end groups","volume":"564","author":"Wang","year":"2019","journal-title":"Int. J. 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Tomogr."},{"key":"2026073101221254100_cit21","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.jconrel.2024.09.045","article-title":"Implant dynamics, inner\nstructure, and their impact on drug release\nof in situ forming implants uncovered through CT imaging","volume":"375","author":"Lin","year":"2024","journal-title":"J. Controlled Release"},{"key":"2026073101221254100_cit22","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.xphs.2024.10.019","article-title":"Evaluation of the impact\nof the polymer end groups and molecular\nweight on in vitro and in vivo performances of PLGA based in situ\nforming implants for ketoprofen","volume":"114","author":"Saha","year":"2025","journal-title":"J. Pharm. Sci."},{"key":"2026073101221254100_cit23","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1002\/jbm.b.33920","article-title":"Mapping intermediate degradation\nproducts of poly(lactic-co-glycolic acid) in vitro","volume":"106","author":"Li","year":"2018","journal-title":"J. Biomed. Mater. Res., Part B"},{"key":"2026073101221254100_cit24","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1021\/acs.molpharmaceut.2c00945","article-title":"Influence of PLGA End Groups on the Release Profile of Dexamethasone\nfrom Ocular Implants","volume":"20","author":"Saraf","year":"2023","journal-title":"Mol. Pharmaceutics"},{"key":"2026073101221254100_cit25","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1163\/156856201744425","article-title":"Synthesis, characterization,\nbiodegradation, and drug delivery application\nof biodegradable lactic\/glycolic acid polymers. Part II: biodegradation","volume":"12","author":"Wu","year":"2001","journal-title":"J. Biomater. Sci., Polym. Ed."},{"key":"2026073101221254100_cit26","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ijpharm.2011.05.049","article-title":"The mechanisms of drug\nrelease in poly(lactic-co-glycolic acid)-based drug delivery systems\u2500A\nreview","volume":"415","author":"Fredenberg","year":"2011","journal-title":"Int. J. Pharm."}],"container-title":["Chemical &amp; Biomedical\nImaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/cbmi.6c00001","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article-pdf\/4\/7\/1509\/66282496\/cbmi.6c00001.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article-pdf\/4\/7\/1509\/66282496\/cbmi.6c00001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:22:16Z","timestamp":1785475336000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article\/4\/7\/1509\/5234128\/Computed-Tomography-Imaging-and-Characteristics-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":26,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,2,17]]},"published-print":{"date-parts":[[2026,7,27]]}},"URL":"https:\/\/doi.org\/10.1021\/cbmi.6c00001","relation":{},"ISSN":["2832-3637"],"issn-type":[{"value":"2832-3637","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]}}}