{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:22:27Z","timestamp":1791919347435,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The current study focuses on the development of innovative and highly-stable curcumin (CUR)-based therapeutics by encapsulating CUR in biocompatible poly(n-butyl acrylate)-block-poly(oligo(ethylene glycol) methyl ether acrylate) (PnBA-b-POEGA) micelles. State-of-the-art methods were used to investigate the encapsulation of CUR in PnBA-b-POEGA micelles and the potential of ultrasound to enhance the release of encapsulated CUR. Dynamic light scattering (DLS), attenuated total reflection Fourier transform infrared (ATR-FTIR), and ultraviolet-visible (UV-Vis) spectroscopies confirmed the successful encapsulation of CUR within the hydrophobic domains of the copolymers, resulting in the formation of distinct and robust drug\/polymer nanostructures. The exceptional stability of the CUR-loaded PnBA-b-POEGA nanocarriers over a period of 210 days was also demonstrated by proton nuclear magnetic resonance (1H-NMR) spectroscopy studies. A comprehensive 2D NMR characterization of the CUR-loaded nanocarriers authenticated the presence of CUR within the micelles, and unveiled the intricate nature of the drug-polymer intermolecular interactions. The UV-Vis results also indicated high encapsulation efficiency values for the CUR-loaded nanocarriers and revealed a significant influence of ultrasound on the release profile of CUR. The present research provides new understanding of the encapsulation and release mechanisms of CUR within biocompatible diblock copolymers and has significant implications for the advancement of safe and effective CUR-based therapeutics.<\/jats:p>","DOI":"10.3390\/ijms24054621","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:00:38Z","timestamp":1677553238000},"page":"4621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Curcumin-Loaded PnBA-b-POEGA Nanoformulations: A Study of Drug-Polymer Interactions and Release Behavior"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8984-4477","authenticated-orcid":false,"given":"Angeliki","family":"Chroni","sequence":"first","affiliation":[{"name":"Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-992X","authenticated-orcid":false,"given":"Thomas","family":"Mavromoustakos","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis, 15771 Zografou, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-7430","authenticated-orcid":false,"given":"Stergios","family":"Pispas","sequence":"additional","affiliation":[{"name":"Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1021\/acs.chemrev.8b00199","article-title":"Block Copolymer Micelles in Nanomedicine Applications","volume":"118","author":"Cabral","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1007\/s00018-004-4153-5","article-title":"Targeted polymeric micelles for delivery of poorly soluble drugs","volume":"61","author":"Torchilin","year":"2004","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.addr.2012.09.026","article-title":"Advanced drug delivery devices via self-assembly of amphiphilic block copolymers","volume":"64","author":"Vandermeulen","year":"2012","journal-title":"Adv. Drug Deliver. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.addr.2012.09.013","article-title":"Block copolymer micelles for drug delivery: Design, characterization and biological significance","volume":"64","author":"Kataoka","year":"2012","journal-title":"Adv. Drug Deliver. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1039\/C5PY01940K","article-title":"Synthesis of amphiphilic block-type macromolecular brushes with cleavable pendant chains and fabrication of micelle-templated polymer nanocapsules","volume":"7","author":"Han","year":"2016","journal-title":"Polym. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1070\/RCR4870","article-title":"Amphiphilic multicomponent molecular brushes","volume":"88","author":"Ivanov","year":"2019","journal-title":"Russ. Chem. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1021\/acs.biomac.7b00443","article-title":"Effect of Molecular Architecture on Cell Interactions and Stealth Properties of PEG","volume":"18","author":"Ozer","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1517\/17425240903158917","article-title":"Biodegradable amphiphilic polymer\u2013drug conjugate micelles","volume":"6","author":"Hu","year":"2009","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20091","DOI":"10.3390\/molecules191220091","article-title":"The chemistry of curcumin: From extraction to therapeutic agent","volume":"19","author":"Priyadarsini","year":"2014","journal-title":"Molecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1016\/j.matpr.2021.01.299","article-title":"Amphiphilic block copolymers as potential drug delivery agent for curcumin: A review","volume":"43","author":"Kumari","year":"2021","journal-title":"Mater. Today Proc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1016\/j.actbio.2008.04.021","article-title":"Synthesis of novel biodegradable and self-assembling methoxy poly (ethylene glycol)\u2013palmitate nanocarrier for curcumin delivery to cancer cells","volume":"4","author":"Sahu","year":"2008","journal-title":"Acta Biomater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1208\/s12248-015-9811-z","article-title":"Therapeutic applications of curcumin nanoformulations","volume":"17","author":"Yallapu","year":"2015","journal-title":"AAPS J."},{"key":"ref_14","first-page":"279","article-title":"Impact of PLA\/PEG ratios on curcumin solubility and encapsulation efficiency, size and release behavior of curcumin loaded poly (lactide)-poly (ethylenglycol) polymeric micelles","volume":"6","author":"Thong","year":"2014","journal-title":"Int. J. Drug Deliv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/21691401.2016.1146736","article-title":"Fabrication of biodegradable PEG\u2013PLA nanospheres for solubility, stabilization, and delivery of curcumin","volume":"45","author":"Liang","year":"2017","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1177\/0883911520944416","article-title":"Enhancing the performance of PEG-b-PCL-based nanocarriers for curcumin through its conjugation with lipophilic biomolecules","volume":"35","author":"Angarita","year":"2020","journal-title":"J. Bioact. Compat. Polym."},{"key":"ref_17","first-page":"300","article-title":"Micelles of poly (ethylene oxide)-b-poly (\u03b5-caprolactone) as vehicles for the solubilization, stabilization, and controlled delivery of curcumin","volume":"86","author":"Ma","year":"2008","journal-title":"J. Biomed. Mater. Res. Part A Off. J. Soc. Biomater. Jpn. Soc. Biomater. Aust. Soc. Biomater. Korean Soc. Biomater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1177\/0885328209357110","article-title":"Encapsulation of curcumin in Pluronic block copolymer micelles for drug delivery applications","volume":"25","author":"Sahu","year":"2011","journal-title":"J. Biomater. Appl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.colsurfb.2012.04.017","article-title":"Curcumin loaded mixed micelles composed of Pluronic P123 and F68: Preparation, optimization and in vitro characterization","volume":"97","author":"Zhao","year":"2012","journal-title":"Colloids Surf. B"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/1061186X.2019.1572158","article-title":"Advances in curcumin-loaded nanopreparations: Improving bioavailability and overcoming inherent drawbacks","volume":"27","author":"Zhang","year":"2019","journal-title":"J. Drug Target."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yavarpour-Bali, H., Ghasemi-Kasman, M., and Pirzadeh, M. (2019). Curcumin-loaded nanoparticles: A novel therapeutic strategy in treatment of central nervous system disorders. Int. J. Nanomed., 4449\u20134460.","DOI":"10.2147\/IJN.S208332"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Riccardi, C., Napolitano, F., Montesarchio, D., Sampaolo, S., and Melone, M.A.B. (2021). Nanoparticle-guided brain drug delivery: Expanding the therapeutic approach to neurodegenerative diseases. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111897"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"o608","DOI":"10.1107\/S0108270104015434","article-title":"Curcumin and derivatives","volume":"60","author":"Mague","year":"2004","journal-title":"Acta Crystallogr. Sect. C Cryst. Struct. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/nrc1189","article-title":"Cancer chemoprevention with dietary phytochemicals","volume":"3","author":"Surh","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S1074-5521(03)00169-8","article-title":"Irreversible inhibition of CD13\/aminopeptidase N by the antiangiogenic agent curcumin","volume":"10","author":"Shim","year":"2003","journal-title":"Chem. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1021\/tx034101x","article-title":"Interplay between MRP inhibition and metabolism of MRP inhibitors: The case of curcumin","volume":"16","author":"Wortelboer","year":"2003","journal-title":"Chem. Res. Toxicol."},{"key":"ref_27","first-page":"81","article-title":"Spectral and photophysical behaviors of curcumin and curcuminoids","volume":"21","author":"Bong","year":"2000","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/jlac.198519850805","article-title":"Synthesis of naturally occurring curcuminoids and related compounds","volume":"1985","author":"Pedersen","year":"1985","journal-title":"Liebigs Ann. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.pnmrs.2016.01.005","article-title":"Applications of NMR spectroscopy to systems biochemistry","volume":"92","author":"Fan","year":"2016","journal-title":"Prog. Nucl. Magn. Reson. Spectrosc."},{"key":"ref_30","first-page":"3742","article-title":"Micellar systems: Nuclear magnetic resonance spectroscopy","volume":"5","author":"Wong","year":"2006","journal-title":"Encycl. Surf. Colloid Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chroni, A., Mavromoustakos, T., and Pispas, S. (2021). Nano-Assemblies from Amphiphilic PnBA-b-POEGA Copolymers as Drug Nanocarriers. Polymers, 13.","DOI":"10.3390\/polym13071164"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chroni, A., Mavromoustakos, T., and Pispas, S. (2020). Biocompatible PEO-b-PCL nanosized micelles as drug carriers: Structure and drug\u2013polymer interactions. Nanomaterials, 10.","DOI":"10.3390\/nano10091872"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3390\/macromol1030014","article-title":"Poly (2-oxazoline)-Based Amphiphilic Gradient Copolymers as Nanocarriers for Losartan: Insights into Drug\u2013Polymer Interactions","volume":"1","author":"Chroni","year":"2021","journal-title":"Macromol"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1900477","DOI":"10.1002\/marc.201900477","article-title":"pH-Driven Morphological Diversity in Poly [n-Butyl Acrylate-block-(2-(Dimethylamino) Ethyl Acrylate)] Amphiphilic Copolymer Solutions","volume":"40","author":"Chroni","year":"2019","journal-title":"Macromol. Rapid Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3329\/jsr.v6i3.18750","article-title":"Synthesis and Characterization of some Ternary Metal Complexes of Curcumin with 1, 10-phenanthroline and their Anticancer Applications","volume":"6","author":"Ismail","year":"2014","journal-title":"J. Sci. Res."},{"key":"ref_36","first-page":"2903","article-title":"Structural investigation on curcumin","volume":"20","author":"Gunasekaran","year":"2008","journal-title":"Asian J. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14293","DOI":"10.3390\/molecules200814293","article-title":"The stability, sustained release and cellular antioxidant activity of curcumin nanoliposomes","volume":"20","author":"Chen","year":"2015","journal-title":"Molecules"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s13205-015-0302-9","article-title":"Curcumin nanoparticles: Physico-chemical fabrication and its in vitro efficacy against human pathogens","volume":"5","author":"Pandit","year":"2015","journal-title":"3 Biotech"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8587","DOI":"10.1038\/s41598-020-65468-1","article-title":"Curcumin encapsulated lecithin nanoemulsions: An oral platform for ultrasound mediated spatiotemporal delivery of curcumin to the tumor","volume":"10","author":"Prasad","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ijpharm.2016.01.029","article-title":"pH-sensitive micelles based on acid-labile pluronic F68\u2013curcumin conjugates for improved tumor intracellular drug delivery","volume":"502","author":"Fang","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"130000","DOI":"10.1016\/j.foodchem.2021.130000","article-title":"Existence of \u03b2-diketone form of curcuminoids revealed by NMR spectroscopy","volume":"360","author":"Prasad","year":"2021","journal-title":"Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ejpb.2014.11.002","article-title":"Tuning the architecture of polymeric conjugate to mediate intracellular delivery of pleiotropic curcumin","volume":"90","author":"Wang","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115101","DOI":"10.1088\/0957-4484\/26\/11\/115101","article-title":"Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery","volume":"26","author":"Cao","year":"2015","journal-title":"Nanotechnology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1007\/s11095-012-0848-8","article-title":"Biodegradable polymer-curcumin conjugate micelles enhance the loading and delivery of low-potency curcumin","volume":"29","author":"Yang","year":"2012","journal-title":"Pharm. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2013.12.010","article-title":"State-of-the-art materials for ultrasound-triggered drug delivery","volume":"72","author":"Sirsi","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"374","DOI":"10.3109\/02656736.2012.665567","article-title":"Ultrasound-mediated micellar drug delivery","volume":"28","author":"Rapoport","year":"2012","journal-title":"Int. J. Hyperth. Off. J. Eur. Soc. Hyperthermic Oncol. North Am. Hyperth. Group"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/978-3-319-22536-4_20","article-title":"Ultrasound-Mediated Polymeric Micelle Drug Delivery","volume":"880","author":"Xia","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9893","DOI":"10.1038\/s41598-018-28140-3","article-title":"Investigation of drug release modulation from poly(2-oxazoline) micelles through ultrasound","volume":"8","author":"Salgarella","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_49","unstructured":"Chroni, A., Chrysostomou, V., Skandalis, A., and Pispas, S. (2021). Supramolecules in Drug Discovery and Drug Delivery, Springer."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1900341","DOI":"10.1002\/macp.201900341","article-title":"Combining ultra-high drug-loaded micelles and injectable hydrogel drug depots for prolonged drug release","volume":"221","author":"Lorson","year":"2020","journal-title":"Macromol. Chem. Phys."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18540","DOI":"10.1002\/anie.201908914","article-title":"Loading-Dependent Structural Model of Polymeric Micelles Encapsulating Curcumin by Solid-State NMR Spectroscopy","volume":"58","author":"Schlauersbach","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1800216","DOI":"10.1002\/marc.201800216","article-title":"Polymeric encapsulation of turmeric extract for bioimaging and antimicrobial applications","volume":"40","author":"Liu","year":"2019","journal-title":"Macromol. Rapid Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"025001","DOI":"10.1088\/2043-6262\/7\/2\/025001","article-title":"Curcumin as fluorescent probe for directly monitoring in vitro uptake of curcumin combined paclitaxel loaded PLA-TPGS nanoparticles","volume":"7","author":"Nguyen","year":"2016","journal-title":"Adv. Nat. Sci. Nanosci. Nanotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4621\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:43:59Z","timestamp":1760121839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,27]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054621"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054621","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,27]]}}}