{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:50:30Z","timestamp":1783511430751,"version":"3.55.0"},"reference-count":135,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Treating brain cancer remains challenging due to the blood\u2013brain barrier (BBB) and the systemic toxicity of chemotherapy. This study focuses on developing human serum albumin (HSA) nanoparticles modified with low-molecular-weight protamine (LMWP) to improve crossing the BBB and enable targeted delivery of curcumin and temozolomide (TMZ). Nanoparticle stability was enhanced by crosslinking with aldehyde groups from oxidized gellan (OG). The successful attachment of LMWP to HSA at the thiol group of Cys34 was confirmed through FT-IR and 1H-NMR analyses. Most self-assembled nanoparticles were smaller than 200 nm in diameter. Curcumin showed higher encapsulation efficiency than TMZ. In vitro drug release was pH-dependent: curcumin released more at pH 7.4, while TMZ release was better at pH 4. Higher crosslinking degrees reduced drug release. Cytotoxicity assays on V79-4 (normal) and C6 (glioma) cell lines showed increased apoptosis and significantly lower IC50 values for co-encapsulated formulations, indicating a synergistic effect. Curcumin\u2019s antioxidant activity was maintained and protected from UV degradation by the polymer matrix. The parallel artificial membrane permeability assay (PAMPA) confirmed that the functionalized formulations with co-encapsulated drugs could cross the BBB. Hemocompatibility studies indicated a favorable profile for intravenous use.<\/jats:p>","DOI":"10.3390\/gels11090708","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T15:15:57Z","timestamp":1756912557000},"page":"708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development of an Innovative Nanosystem Based on Functionalized Albumin and Oxidized Gellan for the Synergistic Delivery of Curcumin and Temozolomide in the Treatment of Brain Cancer"],"prefix":"10.3390","volume":"11","author":[{"given":"Camelia Elena","family":"Iurciuc (Tincu)","sequence":"first","affiliation":[{"name":"Department of Natural and Synthetic Polymers, \u201cCristofor Simionescu\u201d Faculty of Chemical Engineering and Protection of the Environment, \u201cGheorghe Asachi\u201d Technical University, 73, Prof. Dr. Docent Dimitrie Mangeron Street, 700050 Iasi, Romania"},{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Vochi\u021ba","sequence":"additional","affiliation":[{"name":"Institute of Biological Research Iasi, Branch of National Institute of Research and Development for Biological Science, 47, Lascar Catargi Street, 700107 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9601-7928","authenticated-orcid":false,"given":"Daniela","family":"Gherghel","sequence":"additional","affiliation":[{"name":"Institute of Biological Research Iasi, Branch of National Institute of Research and Development for Biological Science, 47, Lascar Catargi Street, 700107 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-5437","authenticated-orcid":false,"given":"Cosmin-Teodor","family":"Mihai","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania"},{"name":"Praxis Medical Investigations, Moara de Vant Street, No. 35, 700376 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vasiliu","sequence":"additional","affiliation":[{"name":"\u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Grigore Ghica Voda Alley, No. 41A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9653-707X","authenticated-orcid":false,"given":"\u0218tefania","family":"Racovi\u021b\u0103","sequence":"additional","affiliation":[{"name":"\u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Grigore Ghica Voda Alley, No. 41A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-3992","authenticated-orcid":false,"given":"Anca Niculina","family":"Cadinoiu","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cApollonia\u201d University of Iasi, 11, Pacurari Street, 700511 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-3583","authenticated-orcid":false,"given":"Corina Lenu\u021ba","family":"Logigan","sequence":"additional","affiliation":[{"name":"Department of Natural and Synthetic Polymers, \u201cCristofor Simionescu\u201d Faculty of Chemical Engineering and Protection of the Environment, \u201cGheorghe Asachi\u201d Technical University, 73, Prof. Dr. Docent Dimitrie Mangeron Street, 700050 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5157-2952","authenticated-orcid":false,"given":"Mihaela","family":"Hamcerencu","sequence":"additional","affiliation":[{"name":"Laboratoire de Photochimie et Ing\u00e9nierie Macromol\u00e9culaires\u2014Ecole Nationale Sup\u00e9rieure de Chimie de Mulhouse, Universit\u00e9 de Haute Alsace, 3 Rue Alfred Werner, 68093 Mulhouse Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florin","family":"Mitu","sequence":"additional","affiliation":[{"name":"Department of Medical Specialties (I), Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, University Street, 700115 Iasi, Romania"},{"name":"Academy of Medical Sciences, I. C. Br\u0103tianu Street, Nr. 1, Sector 3, 030167 Bucharest, Romania"},{"name":"Academy of Romanian Scientists, Ilfov Str., Nr. 3, Sector 5, 050045 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4929-0830","authenticated-orcid":false,"given":"Marcel","family":"Popa","sequence":"additional","affiliation":[{"name":"Department of Natural and Synthetic Polymers, \u201cCristofor Simionescu\u201d Faculty of Chemical Engineering and Protection of the Environment, \u201cGheorghe Asachi\u201d Technical University, 73, Prof. Dr. Docent Dimitrie Mangeron Street, 700050 Iasi, Romania"},{"name":"Academy of Romanian Scientists, Ilfov Str., Nr. 3, Sector 5, 050045 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6447-0958","authenticated-orcid":false,"given":"L\u0103cr\u0103mioara","family":"Ochiuz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, \u201cGrigore T. 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