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The aim of this study was the development of PEG-coated albumin nanoparticles for delivering rapamycin and maintaining its biological activity after encapsulation. Rapamycin-loaded albumin nanoparticles were prepared by desolvation of an aqueous solution of the protein with ethanol and subsequent coating with PEG 35,000. The resulting nanoparticles (NPA-RAP) displayed adequate physicochemical properties for intravenous delivery, including sizes within the tumor-targeting range (150\u2013200 nm), low polydispersity (&amp;lt;0.2), and negative zeta potential (\u223c\u221230 mV). PEGylation and surface charge ensured short-term stability, while encapsulation efficiency exceeded 70%, with sustained biphasic release (40% over 24 h) well described by the Weibull model. In vitro, NPA-RAP showed cytotoxicity in MCF-7 breast cancer cells comparable to free rapamycin but with lower IC50 values. In Caenorhabditis elegans, NPA-RAP did not affect fat content but extended lifespan by \u223c70%, outperforming free rapamycin. These results suggest that these nanoparticles can successfully transport rapamycin without causing detectable carrier-induced toxicity, highlighting its promise for further therapeutic assessment.<\/jats:p>","DOI":"10.1021\/acsomega.6c02977","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:02:02Z","timestamp":1785870122000},"page":"47730-47738","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Human\nSerum Albumin Nanoparticles for\nRapamycin Delivery"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-3513","authenticated-orcid":true,"given":"Camila Fernanda","family":"Rodero","sequence":"first","affiliation":[{"name":"Sa\u0303o Paulo State University , , ,","place":["Araraquara, Brazil, 14800-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pangua","sequence":"additional","affiliation":[{"name":"University of Navarra , , ,","place":["Pamplona, Spain, 31008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Morales","family":"Gracia","sequence":"additional","affiliation":[{"name":"University of Navarra , , ,","place":["Pamplona, Spain, 31008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melibea Berzosa","family":"Suner","sequence":"additional","affiliation":[{"name":"University of Navarra , , ,","place":["Pamplona, Spain, 31008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela Tavares","family":"Guiguer","sequence":"additional","affiliation":[{"name":"Sa\u0303o Paulo State University , , ,","place":["Araraquara, Brazil, 14800-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6698-0545","authenticated-orcid":true,"given":"Marlus","family":"Chorilli","sequence":"additional","affiliation":[{"name":"Sa\u0303o Paulo State University , , ,","place":["Araraquara, Brazil, 14800-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9687-3436","authenticated-orcid":true,"given":"Juan M.","family":"Irache","sequence":"additional","affiliation":[{"name":"University of Navarra , , ,","place":["Pamplona, Spain, 31008"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"2026081811084008800_cit1","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.3390\/biology12091202","article-title":"The Long Scientific Journey of Sirolimus (Rapamycin): From the Soil\nof Easter Island (Rapa Nui) to Applied Research and Clinical Trials\non \u03b2-Thalassemia and Other Hemoglobinopathies","volume":"12","author":"Gambari","year":"2023","journal-title":"Biology"},{"key":"2026081811084008800_cit2","doi-asserted-by":"publisher","first-page":"114498","DOI":"10.1016\/j.ejmech.2022.114498","article-title":"Contemporary mTOR inhibitor\nscaffolds to diseases breakdown: A patent\nreview (2015\u20132021)","volume":"238","author":"Oleksak","year":"2022","journal-title":"Eur. 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Immunol."},{"key":"2026081811084008800_cit5","doi-asserted-by":"publisher","first-page":"6962","DOI":"10.3748\/wjg.v23.i38.6962","article-title":"Delayed and short course\nof rapamycin prevents organ rejection after\nallogeneic liver transplantation in rats","volume":"23","author":"Hamdani","year":"2017","journal-title":"World\nJ. Gastroenterol."},{"key":"2026081811084008800_cit6","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010408","article-title":"MTOR inhibition modulates\nvaccine-induced immune responses\nto generate memory T cells in patients with solid tumors","volume":"13","author":"Withers","year":"2025","journal-title":"J. Immunother. 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