{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:37:22Z","timestamp":1793745442526,"version":"4.6.1"},"reference-count":48,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior","doi-asserted-by":"publisher","award":["88887.837574\/2023-00"],"award-info":[{"award-number":["88887.837574\/2023-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda??o de Amparo ? i Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Paclitaxel (PTX) is a potent antiglioma agent, but its clinical use is limited by poor penetration across the blood\u2013brain barrier (BBB). This study developed and evaluated a nose-to-brain delivery strategy using paclitaxel-loaded hybrid nanoparticles (HNP\u2013PTX) for intranasal administration. A full 22 factorial design was employed to optimize the formulation, yielding an HNP\u2013PTX system with a monodisperse distribution (&amp;lt;200 nm) and spherical morphology. The impact of chitosan coating was evaluated, revealing changes in surface charge and spray properties; but this did not significantly enhance transport across RPMI-2650 cells cultured at the air\u2013liquid interface. Importantly, all HNP\u2013PTX formulations preserved nasal epithelial barrier integrity while significantly increasing PTX permeation relative to the free drug. Cytotoxicity assays in U87-MG glioblastoma cells showed that HNP\u2013PTX reduced cell viability more than both taxol and temozolomide (TMZ). These in vitro findings suggest HNP\u2013PTX is a promising candidate for further in vivo evaluation as an intranasal formulation for glioblastoma treatment.<\/jats:p>","DOI":"10.1021\/acsomega.6c05503","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:50:01Z","timestamp":1788375001000},"page":"54292-54303","source":"Crossref","is-referenced-by-count":1,"title":["Design and Evaluation\nof PLGA-Based Hybrid Nanoparticles\nfor Nasal Paclitaxel Delivery: Formulation Optimization, Barrier Transport,\nand Cytotoxicity Assessment"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5487-1046","authenticated-orcid":true,"given":"Anna Carolina da Silva","family":"Sousa","sequence":"first","affiliation":[{"name":"Federal University of Minas Gerais , , Av. Anto\u0302nio Carlos, 6627 , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Mari Ramos","family":"Oda","sequence":"additional","affiliation":[{"name":"Federal University of Minas Gerais , , Av. Anto\u0302nio Carlos, 6627 , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7641-6585","authenticated-orcid":true,"given":"Andre\u0301 Luis","family":"Branco de Barros","sequence":"additional","affiliation":[{"name":"Federal University of Minas Gerais , , Av. Anto\u0302nio Carlos, 6627 , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0561-2343","authenticated-orcid":true,"given":"Maria Beta\u0302nia","family":"de Freitas Marques","sequence":"additional","affiliation":[{"name":"Federal University of Alfenas , , , ,","place":["Alfenas, Minas Gerais, Brazil, 37130-001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Yuen Jerry","family":"Wong","sequence":"additional","affiliation":[{"name":"Respiratory Technology, Woolcock Institute of Medical Research , , ,","place":["Sydney, New South Wales, Australia, 2037"]},{"name":"Macquarie University , , , ,","place":["Sydney, New South Wales, Australia, 2109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Xin","family":"Ong","sequence":"additional","affiliation":[{"name":"Respiratory Technology, Woolcock Institute of Medical Research , , ,","place":["Sydney, New South Wales, Australia, 2037"]},{"name":"Macquarie University , , , ,","place":["Sydney, New South Wales, Australia, 2109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Traini","sequence":"additional","affiliation":[{"name":"Respiratory Technology, Woolcock Institute of Medical Research , , ,","place":["Sydney, New South Wales, Australia, 2037"]},{"name":"Macquarie University , , , ,","place":["Sydney, New South Wales, Australia, 2109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8812-3811","authenticated-orcid":true,"given":"Elaine Amaral","family":"Leite","sequence":"additional","affiliation":[{"name":"Federal University of Minas Gerais , , Av. Anto\u0302nio Carlos, 6627 , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"issue":"2","key":"2026091516113776600_cit1","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1158\/1078-0432.CCR-19-2182","article-title":"Ultrasound-mediated Delivery of Paclitaxel for Glioma: A Comparative\nStudy of Distribution, Toxicity, and Efficacy of Albumin-bound Versus\nCremophor Formulations","volume":"26","author":"Zhang","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"2026091516113776600_cit2","doi-asserted-by":"publisher","first-page":"1076958","DOI":"10.3389\/fphar.2022.1076958","article-title":"Mechanism of action of paclitaxel\nfor treating glioblastoma based on single-cell RNA sequencing data\nand network pharmacology","volume":"13","author":"Lu","year":"2022","journal-title":"Front. Pharmacol."},{"issue":"7391","key":"2026091516113776600_cit3","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The Cancer Cell Line Encyclopedia enables predictive\nmodelling of\nanticancer drug sensitivity","volume":"483","author":"Barretina","year":"2012","journal-title":"Nature"},{"issue":"3","key":"2026091516113776600_cit4","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1002\/jbm.b.33920","article-title":"Mapping intermediate\ndegradation\nproducts of poly(lactic- co -glycolic acid) in vitro","volume":"106","author":"Li","year":"2018","journal-title":"J. Biomed. Mater. Res., Part B"},{"issue":"7","key":"2026091516113776600_cit5","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1038\/ng.3590","article-title":"Clonal evolution of glioblastoma under therapy","volume":"48","author":"Wang","year":"2016","journal-title":"Nat. Genet."},{"key":"2026091516113776600_cit6","doi-asserted-by":"publisher","first-page":"4509","DOI":"10.2147\/IJN.S165184","article-title":"Magnetic targeting of\npaclitaxel-loaded poly(lactic-co-glycolic acid)-based\nnanoparticles for the treatment of glioblastoma","volume":"13","author":"Ganipineni","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"2026091516113776600_cit7","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jconrel.2018.05.008","article-title":"Drug delivery\nchallenges and future\nof chemotherapeutic nanomedicine for glioblastoma treatment","volume":"281","author":"Ganipineni","year":"2018","journal-title":"J. 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Controlled Release"},{"key":"2026091516113776600_cit14","doi-asserted-by":"publisher","first-page":"629","DOI":"10.3390\/pharmaceutics14030629","article-title":"Evaluation of Recent\nIntranasal Drug Delivery Systems\nto the Central Nervous System","volume":"14","author":"Crowe","year":"2022","journal-title":"Pharmaceutics"},{"issue":"1","key":"2026091516113776600_cit15","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1016\/0378-5173(89)90281-0","article-title":"Nanocapsule formation by interfacial polymer deposition\nfollowing\nsolvent displacement","volume":"55","author":"Fessi","year":"1989","journal-title":"Int. J. 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Soc."},{"key":"2026091516113776600_cit17","volume-title":"ASTM E2550\u201317:\nStandard Test Method for Thermal Stability by Thermogravimetry","author":"ASTM: American Society for Testing and Materials.","year":"2017"},{"key":"2026091516113776600_cit18","volume-title":"ASTM E537\u201312:\nStandard Test Method for Thermal Stability of Chemicals by Differential\nScanning Calorimetry","author":"ASTM: American Society for Testing and Materials.","year":"2012"},{"key":"2026091516113776600_cit19","volume-title":"ASTM-E1356:\nStandard Test Method for Assignment of the Glass Transition Temperatures\nby Differential Calorimetry","author":"ASTM: American Society for Testing and Materials.","year":"2014"},{"key":"2026091516113776600_cit20","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.ejpb.2016.07.010","article-title":"Application of RPMI\n2650 nasal cell model to a 3D printed apparatus\nfor the testing of drug deposition and permeation of nasal products","volume":"107","author":"Pozzoli","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"2026091516113776600_cit21","doi-asserted-by":"publisher","first-page":"369","DOI":"10.3390\/pharmaceutics15020369","article-title":"Co-Encapsulation of Simvastatin and Doxorubicin\ninto pH-Sensitive\nLiposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines","volume":"15","author":"Duarte","year":"2023","journal-title":"Pharmaceutics"},{"issue":"13","key":"2026091516113776600_cit22","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","article-title":"New colorimetric cytotoxicity\nassay for anticancer-drug screening","volume":"82","author":"Skehan","year":"1990","journal-title":"J. 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Sci."},{"issue":"3","key":"2026091516113776600_cit26","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3390\/pharmaceutics10030116","article-title":"Tailoring\nFormulations for Intranasal Nose-to-Brain\nDelivery: A Review on Architecture, Physico-Chemical Characteristics\nand Mucociliary Clearance of the Nasal Olfactory Mucosa","volume":"10","author":"Ga\u0308nger","year":"2018","journal-title":"Pharmaceutics"},{"issue":"4","key":"2026091516113776600_cit27","doi-asserted-by":"publisher","first-page":"481","DOI":"10.3390\/pharmaceutics16040481","article-title":"Nasal Delivery to the\nBrain: Harnessing Nanoparticles for Effective\nDrug Transport","volume":"16","author":"Gandhi","year":"2024","journal-title":"Pharmaceutics"},{"issue":"4","key":"2026091516113776600_cit28","doi-asserted-by":"publisher","first-page":"3390","DOI":"10.3390\/ijms24043390","article-title":"Biomaterials-Enhanced Intranasal\nDelivery of Drugs\nas a Direct Route for Brain Targeting","volume":"24","author":"Marcello","year":"2023","journal-title":"Int.\nJ. Mol. Sci."},{"issue":"1\u20132","key":"2026091516113776600_cit29","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.ijpharm.2008.12.007","article-title":"Enhanced electrostatic\ninteraction between chitosan-modified PLGA\nnanoparticle and tumor","volume":"371","author":"Yang","year":"2009","journal-title":"Int. J. Pharm."},{"issue":"2","key":"2026091516113776600_cit30","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.colsurfb.2011.06.004","article-title":"Development of PEG\u2013PLA\/PLGA\nmicroparticles for\npulmonary drug delivery prepared by a novel emulsification technique\nassisted with amphiphilic block copolymers","volume":"87","author":"Takami","year":"2011","journal-title":"Colloids Surf., B"},{"key":"2026091516113776600_cit31","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.colsurfa.2017.02.054","article-title":"Effects of physicochemical\nproperties of poly(lactide-co-glycolide)\non drug release behavior of hydrophobic drug-loaded nanoparticles","volume":"520","author":"Takeuchi","year":"2017","journal-title":"Colloids Surf. A Physicochem. Eng. Asp"},{"issue":"6","key":"2026091516113776600_cit32","doi-asserted-by":"publisher","first-page":"294","DOI":"10.3390\/medicina55060294","article-title":"Preparation, Optimization,\nand In Vivo Evaluation of Nanoparticle-Based\nFormulation for Pulmonary Delivery of Anticancer Drug","volume":"55","author":"Chishti","year":"2019","journal-title":"Medicina (Kaunas)"},{"issue":"2","key":"2026091516113776600_cit33","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/pharmaceutics10020057","article-title":"Impact of Particle Size\nand Polydispersity Index on the Clinical\nApplications of Lipidic Nanocarrier Systems","volume":"10","author":"Danaei","year":"2018","journal-title":"Pharmaceutics"},{"issue":"1","key":"2026091516113776600_cit34","doi-asserted-by":"publisher","first-page":"18012","DOI":"10.1038\/s41598-023-43689-4","article-title":"Application of ensemble\nmachine learning approach to assess the factors\naffecting size and polydispersity index of liposomal nanoparticles","volume":"13","author":"Hoseini","year":"2023","journal-title":"Sci. Rep."},{"key":"2026091516113776600_cit35","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.actbio.2015.09.032","article-title":"Engineering the lipid\nlayer of lipid\u2013PLGA hybrid nanoparticles\nfor enhanced in vitro cellular uptake and improved stability","volume":"28","author":"Hu","year":"2015","journal-title":"Acta Biomater."},{"issue":"2","key":"2026091516113776600_cit36","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S0168-3659(02)00212-2","article-title":"Paclitaxel-loaded PLGA nanoparticles:\npreparation, physicochemical characterization and in vitro anti-tumoral\nactivity","volume":"83","author":"Fonseca","year":"2002","journal-title":"J. Controlled Release"},{"key":"2026091516113776600_cit37","doi-asserted-by":"publisher","first-page":"4961","DOI":"10.2147\/IJN.S209325","article-title":"Lipid-polymer hybrid\nnanoparticles for controlled delivery of hydrophilic\nand lipophilic doxorubicin for breast cancer therapy","volume":"14","author":"Tahir","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"2026091516113776600_cit38","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37807","article-title":"Conjugation\nof Multiple Proteins Onto the Surface of PLGA\/Lipid Hybrid\nNanoparticles","volume":"113","author":"Hu","year":"2025","journal-title":"J. Biomed. Mater. Res., Part\nA"},{"issue":"6","key":"2026091516113776600_cit39","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1590\/1516-1439.045415","article-title":"Study of Thermal Degradation of PLGA, PLGA\nNanospheres and PLGA\/Maghemite\nSuperparamagnetic Nanospheres","volume":"18","author":"Silva","year":"2015","journal-title":"Mater. Res."},{"issue":"4","key":"2026091516113776600_cit40","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14528","article-title":"Self-Assembled\nnanoparticles of natural bioactive molecules enhance the delivery\nand efficacy of paclitaxel in glioblastoma","volume":"30","author":"Li","year":"2024","journal-title":"CNS Neurosci. Ther."},{"issue":"7","key":"2026091516113776600_cit41","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1517\/17425247.2010.495981","article-title":"Chitosan-based hydrogels for nasal drug delivery: from inserts to\nnanoparticles","volume":"7","author":"Luppi","year":"2010","journal-title":"Expert Opin Drug Deli"},{"issue":"2","key":"2026091516113776600_cit42","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3390\/pharmaceutics6020195","article-title":"Analytical challenges\nand regulatory requirements for nasal drug\nproducts in Europe and the US","volume":"6","author":"Trows","year":"2014","journal-title":"Pharmaceutics"},{"issue":"7","key":"2026091516113776600_cit43","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1002\/jps.20090","article-title":"Evaluation\nof different parameters\nthat affect droplet-size distribution from nasal sprays using the\nMalvern Spraytec","volume":"93","author":"Dayal","year":"2004","journal-title":"J. Pharm. Sci."},{"key":"2026091516113776600_cit44","doi-asserted-by":"publisher","first-page":"126991","DOI":"10.1016\/j.ijpharm.2026.126991","article-title":"The effect of spray\nproperties and inspiratory flow\nrate on regional nasal deposition for pressure-swirl versus soft mist\ndevices","volume":"700","author":"Fong","year":"2026","journal-title":"Int. J. Pharm."},{"issue":"4","key":"2026091516113776600_cit45","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1002\/jps.21924","article-title":"2nd. Intranasal delivery to the central\nnervous system: mechanisms and experimental considerations","volume":"99","author":"Dhuria","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"2026091516113776600_cit46","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.addr.2008.11.002","article-title":"Mucus-penetrating nanoparticles for\ndrug and gene delivery to mucosal tissues","volume":"61","author":"Lai","year":"2009","journal-title":"Adv.\nDrug Delivery Rev."},{"key":"2026091516113776600_cit47","doi-asserted-by":"publisher","first-page":"9217","DOI":"10.1021\/acsnano.5b03876","article-title":"Impact of Surface Polyethylene\nGlycol (PEG) Density on Biodegradable\nNanoparticle Transport in Mucus ex Vivo and Distribution in Vivo","volume":"9","author":"Xu","year":"2015","journal-title":"ACS Nano"},{"issue":"3","key":"2026091516113776600_cit48","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.ejpb.2013.07.002","article-title":"Lipid\u2013polymer hybrid nanoparticles\nas a new generation therapeutic delivery platform: A review","volume":"85","author":"Hadinoto","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c05503","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/36\/54292\/67864026\/acsomega.6c05503.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/36\/54292\/67864026\/acsomega.6c05503.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:11:49Z","timestamp":1789503109000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/36\/54292\/5371410\/Design-and-Evaluation-of-PLGA-Based-Hybrid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,30]]},"references-count":48,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,8,30]]},"published-print":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c05503","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,30]]}}}