{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T10:29:37Z","timestamp":1794479377864,"version":"4.9.1"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004916","name":"Foundation for Research Support of Amazonas State","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004916","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006601","name":"Government of Italy Ministry of Foreign Affairs and International Cooperation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006601","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine & Pharmacotherapy"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.biopha.2026.119367","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T20:03:21Z","timestamp":1776456201000},"page":"119367","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["PEG-PCL nanoparticles loaded with amazonian compounds inhibit Zika virus replication and modulate host immune responses"],"prefix":"10.1016","volume":"199","author":[{"given":"Alice","family":"de Freitas Gomes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Dal","family":"Poggetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6957-2205","authenticated-orcid":false,"given":"Carlos Eduardo","family":"de Castro Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa Raquel Silva","family":"Maciel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Campos","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Gomez","family":"d\u2019Ayala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-8991","authenticated-orcid":false,"given":"Catarina","family":"Marques-Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Correa","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary Aparecida","family":"Roque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Massayoshi","family":"Nunomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Cleomir","family":"Pinheiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Danniel","family":"Pinheiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-6801","authenticated-orcid":false,"given":"Samanta","family":"da Silva G\u00fcndel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza Abrah\u00e3o","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1119-7238","authenticated-orcid":false,"given":"Rita de C\u00e1ssia","family":"Saraiva Nunomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Gomes","family":"Naveca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-7662","authenticated-orcid":false,"given":"Anna","family":"Calarco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierfrancesco","family":"Cerruti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9001-7954","authenticated-orcid":false,"given":"Gemilson Soares","family":"Pontes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.biopha.2026.119367_bib1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1186\/s12985-024-02547-z","article-title":"Zika virus tropism and pathogenesis: understanding clinical impacts and transmission dynamics","volume":"21","author":"Tajik","year":"2024","journal-title":"Virol. J."},{"issue":"6","key":"10.1016\/j.biopha.2026.119367_bib2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0130062","article-title":"Novel broad spectrum inhibitors targeting the flavivirus methyltransferase","volume":"10","author":"Brecher","year":"2015","journal-title":"PLoS One"},{"issue":"7","key":"10.1016\/j.biopha.2026.119367_bib3","doi-asserted-by":"crossref","first-page":"919","DOI":"10.15252\/embj.201696241","article-title":"The crystal structure of Zika virus NS5 reveals conserved drug targets","volume":"36","author":"Duan","year":"2017","journal-title":"EMBO J."},{"key":"10.1016\/j.biopha.2026.119367_bib4","doi-asserted-by":"crossref","unstructured":"M. Hennessey, M. Fischer, J.E. StaplesZika virus spreads to new areas - region of the americas, may 2015-january 2016 3 65 MMWR Morb. Mortal. Wkly Rep.2016 , 555810.15585\/mmwr.mm6503e1PMID: 26820163.","DOI":"10.15585\/mmwr.mm6503e1er"},{"issue":"6","key":"10.1016\/j.biopha.2026.119367_bib5","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s15010-016-0935-6","article-title":"Zika virus disease: a current review of the literature","volume":"44","author":"Atif","year":"2016","journal-title":"Infection"},{"issue":"n. 1","key":"10.1016\/j.biopha.2026.119367_bib6","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev-pharmtox-010617-052703","article-title":"The ethnopharmacologic contribution to bioprospecting natural products","volume":"v. 58","author":"BUENZ","year":"2018","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.biopha.2026.119367_bib7","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.antiviral.2018.11.011","article-title":"Tomatidine, a novel antiviral compound towards dengue virus","volume":"161","author":"Diosa-Toro","year":"2019","journal-title":"Antivir. Res"},{"key":"10.1016\/j.biopha.2026.119367_bib8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/molecules26030607","article-title":"Antiviral activity of jamaican medicinal plants and isolated bioactiv compounds","volume":"26","author":"Lowe","year":"2021","journal-title":"Molecules"},{"key":"10.1016\/j.biopha.2026.119367_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.micpath.2020.104563","article-title":"Antiviral activity of astragaloside II, astragaloside III and astragaloside IV compounds against dengue virus: computational docking and in vitro studies","volume":"152","author":"Indu","year":"2021","journal-title":"Microb. Pathog."},{"key":"10.1016\/j.biopha.2026.119367_bib10","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s43450-020-00092-8","article-title":"Nanoemulsion loaded with volatile oil from piper alatipetiolatum as an alternative agent in the control of aedes aegypti","volume":"30","author":"De Oliveira","year":"2020","journal-title":"Rev. Bras. Farm."},{"issue":"5","key":"10.1016\/j.biopha.2026.119367_bib11","doi-asserted-by":"crossref","first-page":"947","DOI":"10.3390\/molecules29050947","article-title":"Chemical composition of piper nigrum l. cultivar guajarina essential oils and their biological activity","volume":"29","author":"Feitosa","year":"2024","journal-title":"Molecules"},{"issue":"11","key":"10.1016\/j.biopha.2026.119367_bib12","first-page":"557","article-title":"Formulation and nanotechnology-based approaches for solubility and bioavailability enhancement of zerumbone","volume":"56","author":"Kesharwani","year":"2020","journal-title":"Med."},{"key":"10.1016\/j.biopha.2026.119367_bib13","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/3237983","article-title":"Zerumbone promotes cytotoxicity in human malignant glioblastoma cells through reactive oxygen species (ROS) _neration","volume":"2020","author":"Jalili-Nik","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"10.1016\/j.biopha.2026.119367_bib14","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.652860","article-title":"Zerumbone suppresses the lps-induced inflammatory response and represses activation of the nlrp3 inflammasome in macrophages","volume":"12","author":"Su","year":"2021","journal-title":"Front Pharm."},{"issue":"16","key":"10.1016\/j.biopha.2026.119367_bib15","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.3390\/molecules25163731","article-title":"Polymeric Nanoparticles: production, characterization, toxicology and ecotoxicology","volume":"25","author":"Zieli\u0144ska","year":"2020","journal-title":"Molecules"},{"key":"10.1016\/j.biopha.2026.119367_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.118761","article-title":"Nano-based approaches in the development of antiviral agents and vaccines","volume":"265","author":"Li","year":"2021","journal-title":"Life Sci."},{"key":"10.1016\/j.biopha.2026.119367_bib17","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jconrel.2021.08.011","article-title":"Nanomedicine based approaches for combating viral infections","volume":"338","author":"Shah","year":"2021","journal-title":"J. Control Release"},{"issue":"10","key":"10.1016\/j.biopha.2026.119367_bib18","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1007\/s13346-021-01090-6","article-title":"Biodegradable nanoparticles combining cancer cell targeting and anti-angiogenic activity for synergistic chemotherapy in epithelial cancer","volume":"12","author":"Moret","year":"2022","journal-title":"Drug Deliv. Transl. Res."},{"key":"10.1016\/j.biopha.2026.119367_bib19","article-title":"An overview of functional nanoparticles as novel emerging antiviral therapeutic agents","volume":"12","author":"Lu","year":"2020","journal-title":"Materials Science Engineering C"},{"issue":"1","key":"10.1016\/j.biopha.2026.119367_bib20","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s12906-018-2360-0","article-title":"Zerumbone from Zingiber zerumbet (L.) smith: a potential prophylactic and therapeutic agent against the cariogenic bacterium Streptococcus mutans","volume":"18","author":"Moreira da Silva","year":"2018","journal-title":"BMC Complement Alter. Med"},{"issue":"7","key":"10.1016\/j.biopha.2026.119367_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0255314","article-title":"Zika virus isolation, propagation, and quantification using multiple methods","volume":"16","author":"Dangsagul","year":"2021","journal-title":"PLoS One"},{"key":"10.1016\/j.biopha.2026.119367_bib22","article-title":"6-Ishwarone: a novel eco-friendly botanical biocide inducing oxidative stress and disrupting defense enzyme activities in Aedes aegypti Linnaeus, 1762 and Anopheles darlingi Root, 1926 (Culicidae)","volume":"6","author":"de Oliveira","year":"2025","journal-title":"Biocatal. Agric. Biotechnol."},{"key":"10.1016\/j.biopha.2026.119367_bib23","volume":"20","author":"Oliveira","year":"2025","journal-title":"ChemicoBiologicaInteractions"},{"key":"10.1016\/j.biopha.2026.119367_bib24","doi-asserted-by":"crossref","DOI":"10.1590\/1678-4324-2018180004","article-title":"Probing the pharmacological parameters, molecular docking and quantum computations of plant derived compounds exhibiting strong inhibitory potential against NS5 from Zika Virus","volume":"61","author":"Rasool","year":"2018","journal-title":"Braz. Arch. Biol. Technol."},{"key":"10.1016\/j.biopha.2026.119367_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2021.111656","article-title":"\u03b1-amyrin-loaded nanocapsules produce selective cytotoxic activity in leukemic cells","volume":"139","author":"Neto","year":"2021","journal-title":"Biomed. Pharm."},{"key":"10.1016\/j.biopha.2026.119367_bib26","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jsps.2018.10.003","article-title":"Cassia grandis Lf nanodispersion is a hypoglycemic product with a potent \u03b1-glucosidase and pancreatic lipase inhibitor effect","volume":"27","author":"Prada","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"10.1016\/j.biopha.2026.119367_bib27","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s43450-020-00085-7","article-title":"Chemical Characterization and Anti-inflammatory Assessment of the Hydroethanolic Extract of Fridericia chica","volume":"30","author":"Takenaka","year":"2020","journal-title":"Rev. Bras. Farm"},{"issue":"1","key":"10.1016\/j.biopha.2026.119367_bib28","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s12943-025-02410-x","article-title":"PEGylated PLGA nanoparticles: unlocking advanced strategies for cancer therapy","volume":"24","author":"Kesharwani","year":"2025","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.biopha.2026.119367_bib29","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.2147\/IJN.S45313","article-title":"S.K. Zerumbone-loaded nanostructured lipid carriers: Preparation, characterization, and antileukemic effect","volume":"8","author":"Rahman","year":"2013","journal-title":"Int. J. Nanomed."},{"issue":"1","key":"10.1016\/j.biopha.2026.119367_bib30","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/s12876-023-02962-6","article-title":"Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS\/NF-\u03baB pathway","volume":"23","author":"Zhang","year":"2023","journal-title":"BMC Gastroenterol."},{"issue":"25","key":"10.1016\/j.biopha.2026.119367_bib31","doi-asserted-by":"crossref","first-page":"15775","DOI":"10.1039\/D2RA00905F","article-title":"Antiviral activity of chitosan nanoparticles encapsulating silymarin (Sil-CNPs) against SARS-CoV-2 (in silico and in vitro study)","volume":"12","author":"Loutfy","year":"2022","journal-title":"RSC Adv."},{"issue":"9","key":"10.1016\/j.biopha.2026.119367_bib32","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3390\/pharmaceutics17091229","article-title":"Antiviral activity of liposomes containing natural compounds against CHIKV","volume":"17","author":"Calmon","year":"2025","journal-title":"Pharmaceutics"},{"issue":"4","key":"10.1016\/j.biopha.2026.119367_bib33","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3390\/v16040629","article-title":"Exploring zika virus impact on endothelial permeability: insights into transcytosis mechanisms and vascular leakage","volume":"16","author":"Henrio Marcellin","year":"2024","journal-title":"Viruses"},{"issue":"1","key":"10.1016\/j.biopha.2026.119367_bib34","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/ana.24839","article-title":"Immune activation in amniotic fluid from zika virus-associated microcephaly","volume":"81","author":"Ornelas","year":"2017","journal-title":"Ann. Neurol."},{"issue":"2","key":"10.1016\/j.biopha.2026.119367_bib35","doi-asserted-by":"crossref","first-page":"577","DOI":"10.4049\/jimmunol.2100179","article-title":"Papel do complexo IL-6-IL-27 na resposta imune antiviral do hospedeiro","volume":"207","author":"Zuo","year":"2021","journal-title":"J. Immunol. 15 De. julho De."},{"key":"10.1016\/j.biopha.2026.119367_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbrc.2024.150455","article-title":"Interleukin-8 in HepG2 cells: Enhancing antiviral proteins in uninfected cells but promoting HBV replication in infected cells","volume":"734","author":"Yang","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"13","key":"10.1016\/j.biopha.2026.119367_bib37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1167\/iovs.64.13.19","article-title":"IL-8 triggers neutrophil extracellular trap formation through an nicotinamide adenine dinucleotide phosphate oxidase- and mitogen-activated protein kinase pathway-dependent mechanism in uveitis","volume":"64","author":"Shu","year":"2023","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.biopha.2026.119367_bib38","article-title":"Immunomodulation of Zerumbone via Decreasing the Production of Reactive Oxygen Species from Immune Cells","author":"Albaayit","year":"2018","journal-title":"Evid. Based Complement Altern. Med"},{"key":"10.1016\/j.biopha.2026.119367_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.652860","article-title":"Zerumbone Suppresses the LPS-Induced Inflammatory Response via Modulating NF-\u03baB and NLRP3 Pathways","volume":"12","author":"Su","year":"2021","journal-title":"Front Pharm."},{"key":"10.1016\/j.biopha.2026.119367_bib40","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.1039\/C7FO00595D","article-title":"Exploring the immunomodulatory and anticancer properties of zerumbone","volume":"8","author":"Haque","year":"2017","journal-title":"Food Funct."},{"key":"10.1016\/j.biopha.2026.119367_bib41","unstructured":"S S., D A., V R.. MCP-1: Function, regulation, and involvement in disease. PubMed [Internet]. [citado 27 de novembro de 2025]; Dispon\u00edvel em: \u3008https:\/\/pubmed.ncbi.nlm.nih.gov\/34233864\/\u3009."},{"issue":"3","key":"10.1016\/j.biopha.2026.119367_bib42","doi-asserted-by":"crossref","first-page":"718","DOI":"10.3390\/jcm9030718","article-title":"Biphasic dose-response induced by phytochemicals: experimental evidence","volume":"9","author":"Jodynis-Liebert","year":"2020","journal-title":"J. Clin. Med."},{"issue":"1","key":"10.1016\/j.biopha.2026.119367_bib43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3390\/ijms24010095","article-title":"The Anti-Inflammatory and Immunomodulatory Activities of Natural Products to Control Autoimmune Inflammation","volume":"24","author":"Moudgil","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"11","key":"10.1016\/j.biopha.2026.119367_bib44","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.3390\/biomedicines9111522","article-title":"Immunomodulatory effects of a concoction of natural bioactive compounds-mechanistic insights","volume":"9","author":"Gangwar","year":"2021","journal-title":"Biomedicines"},{"key":"10.1016\/j.biopha.2026.119367_bib45","unstructured":"Es S., G K. Immunomodulatory and antitumor activity of Piper longum Linn. and piperine. PubMed [Internet]. [citado 27 de novembro de 2025]; Dispon\u00edvel em: \u3008https:\/\/pubmed.ncbi.nlm.nih.gov\/15013199\/\u3009."}],"container-title":["Biomedicine & Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332226004002?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332226004002?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T09:50:12Z","timestamp":1794477012000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332226004002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":45,"alternative-id":["S0753332226004002"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2026.119367","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PEG-PCL nanoparticles loaded with amazonian compounds inhibit Zika virus replication and modulate host immune responses","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2026.119367","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"119367"}}