{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:52:22Z","timestamp":1791157942017,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["US\u20101263053"],"award-info":[{"award-number":["US\u20101263053"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Atherosclerosis, a chronic inflammatory disease characterised by lipid accumulation and endothelial dysfunction, remains a leading cause of cardiovascular morbidity and mortality. While cannabinoid 2 (CB\n                      <jats:sub>2<\/jats:sub>\n                      ) receptor agonists show therapeutic promise in preclinical studies, their systemic application is hindered by poor bioavailability and off\u2010target effects. Consequently, targeted delivery systems are essential to enhance therapeutic efficacy and mitigate adverse effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      This study presents a targeted nanotherapeutic strategy for localising the CB\n                      <jats:sub>2<\/jats:sub>\n                      receptor agonist directly at atherosclerotic lesions. Poly(lactic\u2010co\u2010glycolic acid) (PLGA) nanoparticles (NPs), encapsulating the selective agonist JWH\u2010133 and functionalised with a VCAM\u20101 binding peptide (VBP) for selective binding to vascular cell adhesion molecule\u20101 (VCAM\u20101) (VBP\u2010JWH\u2010133\u2010NPs), were developed. In vivo experiments were conducted in both male and female apolipoprotein E\u2010deficient (ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice to assess the anti\u2010inflammatory and lipid\u2010modulating effects of the nanotherapy. Serum lipid profiles, aortic plaque burden and key inflammatory markers were analysed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>VBP\u2010JWH\u2010133\u2010NPs significantly reduced foam cell\u2010rich depositions and modulate systemic inflammatory markers in both sexes, demonstrating superior anti\u2010atherogenic efficacy compared with free JWH\u2010133. The therapeutic benefits are notably more pronounced in male mice, which exhibit greater initial plaque area and lipid deposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These findings underscore the potential of VBP\u2010JWH\u2010133\u2010NPs as an efficient and superior delivery system for cannabinoid therapies in atherosclerosis. By addressing sex as a biological variable, this approach offers a nuanced strategy for developing more effective and precise cardiovascular interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70688","type":"journal-article","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:31:01Z","timestamp":1791156661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted delivery of the CB\n                    <sub>2<\/sub>\n                    receptor agonist JWH\u2010133 via VCAM\u20101\u2010functionalised nanoparticles attenuates atherosclerosis and reveals sex\u2010specific therapeutic outcomes"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5534-6955","authenticated-orcid":false,"given":"Luc\u00eda","family":"Mart\u00edn\u2010Navarro","sequence":"first","affiliation":[{"name":"Departamento de Farmacia y Tecnolog\u00eda Farmac\u00e9utica, Facultad de Farmacia Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1447-6125","authenticated-orcid":false,"given":"Luc\u00eda","family":"Mart\u00edn\u2010Banderas","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia y Tecnolog\u00eda Farmac\u00e9utica, Facultad de Farmacia Universidad de Sevilla  Sevilla Spain"},{"name":"Instituto de Biomedicina de Sevilla (IBIS) Hospital Universitario Virgen del Roc\u00edo  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3525-8488","authenticated-orcid":false,"given":"Josefa","family":"\u00c1lvarez\u2010Fuentes","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia y Tecnolog\u00eda Farmac\u00e9utica, Facultad de Farmacia Universidad de Sevilla  Sevilla Spain"},{"name":"Instituto de Biomedicina de Sevilla (IBIS) Hospital Universitario Virgen del Roc\u00edo  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7231-9537","authenticated-orcid":false,"given":"Mar\u00eda Dolores","family":"Herrera\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Farmacia Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41371-019-0273-0"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-07166-8"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70230"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70234"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70235"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.009099"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2017.07.010"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00217.2016"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.140"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_13_12_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/978-3-030-57456-7_13","volume-title":"Biodegradable nanoparticles for specific drug transport BT\u2014New trends in macromolecular and supramolecular chemistry for biological applications","author":"Danz K.","year":"2021"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c00216"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-05301-z"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37916"},{"key":"e_1_2_13_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.indcrop.2021.113345","article-title":"Development of enhanced drug delivery vehicles for three cannabis\u2010based terpenes using poly (lactic\u2010co\u2010glycolic acid) based nanoparticles","volume":"164","author":"El\u2010Hammadi M. 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