{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:35:04Z","timestamp":1784550904350,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Breakthrough T1D","award":["3-SRA-2023-1439-S-B"],"award-info":[{"award-number":["3-SRA-2023-1439-S-B"]}]},{"DOI":"10.13039\/100001078","name":"Diabetes Research Institute Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001078","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Glucocorticoids are an important class of therapeutics used in a variety of applications, including allotransplantations. Dexamethasone (Dexa) is well-known for its strong anti-inflammatory, immunosuppressive, and anticancer properties. However, its clinical use is often limited by its poor water solubility, poor pharmacokinetics, and high likelihood of systemic side effects. Methods: To address the issues, we tested a combined strategy where our original Drug-Integrating Amphiphilic Nano-Assemblies (DIANAs), a class of self-assembling polymeric nanoparticles designed for controlled drug release, were used to solubilize and deliver dexamethasone palmitate (DexP), a hydrophobic prodrug of dexamethasone. Results: The palmitate chains of the prodrug can form strong van der Waals interactions with the hydrophobic moieties of the PEG-PPS block copolymer used here. In water, this resulted in the self-assembling of stable dexamethasone palmitate\u2013PEG\u2013PPS nanomicelles, termed DexP-nMICs, with a 25 nm average diameter that slowly released Dexa over more than two weeks. Conclusions: Here we demonstrated that DexP-nMICs can carry elevated amounts of Dexa\u2014increasing its solubility in water\u2014prolong circulation in its pharmacologically active form in vivo and provide passive targeting to inflammation sites. The anti-inflammatory efficacy of DexP-nMICs was first confirmed in vitro on stimulated macrophages, demonstrating a significant reduction in cytokine secretion. An allogeneic mouse skin transplant model, used to assess the therapeutic potential of DexP-nMICs in vivo, confirmed its ability to provide graft-targeted delivery and prolong graft survival as compared to the unformulated parent drug. Therefore, DexP-nMICs are a promising candidate for sustained and localized use of anti-inflammatory drugs in cell and tissue transplantations.<\/jats:p>","DOI":"10.3390\/pharmaceutics17101337","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:29:38Z","timestamp":1760599778000},"page":"1337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Drug-Integrating Amphiphilic Nano-Assemblies: 3. PEG-PPS\/Palmitate Nanomicelles for Sustained and Localized Delivery of Dexamethasone in Cell and Tissue Transplantations"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6663-6371","authenticated-orcid":false,"given":"Giulio","family":"Palummieri","sequence":"first","affiliation":[{"name":"Diabetes Research Institute, School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-1482","authenticated-orcid":false,"given":"Saeida","family":"Saadat","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Ting","family":"Chuang","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2732-8180","authenticated-orcid":false,"given":"Peter","family":"Buchwald","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Department of Molecular and Cellular Pharmacology, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4140-9083","authenticated-orcid":false,"given":"Diana","family":"Velluto","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s40259-025-00703-7","article-title":"Islet cell replacement and regeneration for type 1 diabetes: Current developments and future prospects","volume":"39","author":"Lanzoni","year":"2025","journal-title":"BioDrugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1074-7613(02)00338-2","article-title":"Autoreactive CD8 T cells in organ-specific autoimmunity: Emerging targets for therapeutic intervention","volume":"17","author":"Liblau","year":"2002","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1007\/s00125-023-05970-z","article-title":"Islet autoimmunity in human type 1 diabetes: Initiation and progression from the perspective of the beta cell","volume":"66","author":"Thompson","year":"2023","journal-title":"Diabetologia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1016\/S0140-6736(23)00223-4","article-title":"Type 1 diabetes","volume":"401","author":"Quattrin","year":"2023","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.2337\/diacare.27.6.1506","article-title":"Diabetes complications","volume":"27","author":"Bloomgarden","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1056\/NEJMoa1310799","article-title":"Changes in diabetes-related complications in the United States, 1990\u20132010","volume":"370","author":"Gregg","year":"2014","journal-title":"N. 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