{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:49:34Z","timestamp":1772729374100,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T00:00:00Z","timestamp":1565395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/EQU\/00511\/2019"],"award-info":[{"award-number":["UID\/EQU\/00511\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PD\/BD\/105984\/2014"],"award-info":[{"award-number":["PD\/BD\/105984\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-006939"],"award-info":[{"award-number":["POCI-01-0145-FEDER-006939"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["LEPABE-2-ECO-INNOVATION\u201d \u2013 NORTE\u201001\u20100145\u2010FEDER\u2010000005"],"award-info":[{"award-number":["LEPABE-2-ECO-INNOVATION\u201d \u2013 NORTE\u201001\u20100145\u2010FEDER\u2010000005"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Poly(d,l-lactic-co-glycolic) (PLGA) nanoparticles (NPs) have been widely studied for several applications due to their advantageous properties, such as biocompatibility and biodegradability. Therefore, these nanocarriers could be a suitable approach for glioblastoma multiforme (GBM) therapy. The treatment of this type of tumours remains a challenge due to intrinsic resistance mechanisms. Thus, new approaches must be envisaged to target GBM tumour cells potentially providing an efficient treatment. Co-delivery of temozolomide (TMZ) and O6-benzylguanine (O6BG), an inhibitor of DNA repair, could provide good therapeutic outcomes. In this work, a fractional factorial design (FFD) was employed to produce an optimal PLGA-based nanoformulation for the co-loading of both molecules, using a reduced number of observations. The developed NPs exhibited optimal physicochemical properties for brain delivery (dimensions below 200 nm and negative zeta potential), high encapsulation efficiencies (EE) for both drugs, and showed a sustained drug release for several days. Therefore, the use of an FFD allowed for the development of a nanoformulation with optimal properties for the co-delivery of TMZ and O6BG to the brain.<\/jats:p>","DOI":"10.3390\/pharmaceutics11080401","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T06:38:02Z","timestamp":1565591882000},"page":"401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Factorial Design as a Tool for the Optimization of PLGA Nanoparticles for the Co-Delivery of Temozolomide and O6-Benzylguanine"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2428-7520","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Ramalho","sequence":"first","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"given":"Joana A.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"given":"Manuel A. N.","family":"Coelho","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"given":"Maria Carmo","family":"Pereira","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.biomaterials.2016.12.027","article-title":"Nanoparticles for multi-modality cancer diagnosis: Simple protocol for self-assembly of gold nanoclusters mediated by gadolinium ions","volume":"120","author":"Hou","year":"2017","journal-title":"Biomaterials"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jenvman.2016.05.001","article-title":"Enhanced sonocatalysis of textile wastewater using bentonite-supported ZnO nanoparticles: Response surface methodological approach","volume":"179","author":"Jorfi","year":"2016","journal-title":"J. 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