{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:02:39Z","timestamp":1787029359199,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development","award":["TKP2021-EGA"],"award-info":[{"award-number":["TKP2021-EGA"]}]},{"name":"Innovation Fund","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]},{"name":"Innovation Fund","award":["TKP2021-EGA"],"award-info":[{"award-number":["TKP2021-EGA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The current research aims to develop thermosensitive polymeric micelles loaded with risperidone for nasal administration, emphasizing the added benefits of their thermosensitive behavior under nasal conditions. An initial risk assessment facilitated the advanced development process, confirming that the key indicators of thermosensitivity were suitable for nasal application. The polymeric micelles exhibited an average size of 118.4 \u00b1 3.1 nm at ambient temperature and a size of 20.47 \u00b1 1.2 nm at 36.5 \u00b0C, in both cases in monodisperse distribution. Factors such as pH and viscosity did not significantly impact these parameters, demonstrating appropriate nasal applicability. The model formulations showed a rapid, burst-like drug release profile in vitro, accompanied by a quick and high permeation rate at nasal conditions. Overall, the Quality by Design-based risk assessment process led to the development of an advanced drug delivery system capable of administering risperidone through the nasal cavity.<\/jats:p>","DOI":"10.3390\/pharmaceutics16060703","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T05:36:06Z","timestamp":1716528966000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Risperidone-Loaded Nasal Thermosensitive Polymeric Micelles: Quality by Design-Based Formulation Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0131-4728","authenticated-orcid":false,"given":"Bence","family":"Sipos","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, E\u00f6tv\u00f6s Street 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1564-4813","authenticated-orcid":false,"given":"G\u00e1bor","family":"Katona","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, E\u00f6tv\u00f6s Street 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0807-2781","authenticated-orcid":false,"given":"Ildik\u00f3","family":"Cs\u00f3ka","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, E\u00f6tv\u00f6s Street 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrneurol.2012.76","article-title":"Nanotechnology\u2013novel therapeutics for CNS disorders","volume":"8","author":"Srikanth","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.biopha.2018.12.133","article-title":"Applications of nanotechnology in drug delivery to the central nervous system","volume":"111","author":"Saeedi","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1901589","DOI":"10.1002\/adhm.201901589","article-title":"Antioxidants and nanotechnology: Promises and limits of potentially disruptive approaches in the treatment of central nervous system diseases","volume":"9","author":"Martinelli","year":"2020","journal-title":"Adv. Healthc. Mat."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chountoulesi, M., and Demetzos, C. (2020). Promising nanotechnology approaches in treatment of autoimmune diseases of central nervous system. Brain Sci., 10.","DOI":"10.3390\/brainsci10060338"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1749-6632.2009.05361.x","article-title":"Nanotechnology applications and approaches for neurodegeneration and drug delivery to the central nervous system","volume":"1199","author":"Silva","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jddst.2019.03.022","article-title":"Nanotechnology approaches for enhanced CNS delivery in treating Alzheimer\u2019s disease","volume":"51","author":"Arya","year":"2019","journal-title":"J. Drug Del. Sci. Tech."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Perumal, S., Atchudan, R., and Lee, W. (2022). A review of polymeric micelles and their applications. Polymers, 14.","DOI":"10.3390\/polym14122510"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sipos, B., Katona, G., and Cs\u00f3ka, I. (2021). A systematic, knowledge space-based proposal on quality by design-driven polymeric micelle development. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050702"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ijpharm.2017.09.005","article-title":"Polymeric micelles: Basic research to clinical practice","volume":"532","author":"Deshmukh","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_10","first-page":"1245","article-title":"Polymeric micelle stability","volume":"6","author":"Owen","year":"2012","journal-title":"Nano Today"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.2217\/nnm.11.91","article-title":"Thermosensitive polymeric micelles for targeted drug delivery","volume":"6","author":"Talelli","year":"2011","journal-title":"Nanomedicine"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Abuwatfa, W.H., Awas, N.S., Pitt, W.G., and Husseini, G.A. (2022). Thermosensitive polymers and thermo-responsive liposomal drug delivery systems. Polymers, 14.","DOI":"10.3390\/polym14050925"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101523","DOI":"10.1016\/j.jddst.2020.101523","article-title":"Stimuli-responsive polymeric micelles for the delivery of paclitaxel","volume":"56","author":"Yang","year":"2020","journal-title":"J. Drug Del. Sci. Tech."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/09205063.2020.1854413","article-title":"Synthesis and characterization of PLGA-PEG-PLGA based thermosensitive polyurethane micelles for potential drug delivery","volume":"32","author":"Wang","year":"2020","journal-title":"J. Biomat. Sci. Polym. Ed."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., Streltsov, D.A., Ezhoy, A.A., and Kudryashova, E.V. (2023). Smart pH-and temperature-sensitive micelles based on chitosan grafted with fatty acids to increase the efficiency and selectivity of doxorubicin and its adjuvant regarding the tumor cells. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15041135"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120994","DOI":"10.1016\/j.ijpharm.2021.120994","article-title":"Progress in nasal drug delivery systems","volume":"607","author":"Laffleur","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hussein, N.R., Ome, H.K., Elhissi, A.M., and Ahmed, W. (2020). Advances in nasal drug delivery systems. Adv. Med. Surg. Eng., 279\u2013311.","DOI":"10.1016\/B978-0-12-819712-7.00015-2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2000076","DOI":"10.1002\/adtp.202000076","article-title":"Polymeric nanoparticles for nasal drug delivery to the brain: Relevance to Alzheimer\u2019s disease","volume":"4","author":"Rabiee","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lee, D., and Minko, T. (2021). Nanotherapeutics for nose-to-brain drug delivery: An approach to bypass the blood brain barrier. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122049"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102642","DOI":"10.1016\/j.jddst.2021.102642","article-title":"Recent progress in nanocarriers for direct nose to brain drug delivery","volume":"64","author":"Emad","year":"2021","journal-title":"J. Drug Del. Sci. Tech."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.31351\/vol31iss1pp43-56","article-title":"Improvement of the solubility and dissolution characteristics of risperidone via nanosuspension formulations","volume":"31","author":"Emad","year":"2022","journal-title":"Iraqi J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103751","DOI":"10.1016\/j.drugpo.2022.103751","article-title":"Patient perceptions of higher-dose naloxone nasal spray for opioid overdose","volume":"106","author":"Strickland","year":"2022","journal-title":"Int. J. Drug Policy"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"La Sala, L., and Pontiroli, A.E. (2021). New fast acting glucagon for recovery from hypoglycemia, a life-threatening situation: Nasal powder and injected stable solutions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910643"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ijpharm.2008.03.029","article-title":"Intranasal nanoemulsion based brain targeting drug delivery system of risperidone","volume":"358","author":"Kumar","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3109\/1061186X.2010.523787","article-title":"Brain targeting of risperidone-loaded solid lipid nanoparticles by intranasal route","volume":"19","author":"Patel","year":"2010","journal-title":"J. Drug Targ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.lfs.2016.08.033","article-title":"Development of risperidone liposomes for brain targeting through intranasal route","volume":"163","author":"Narayan","year":"2016","journal-title":"Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"122594","DOI":"10.1016\/j.ijpharm.2023.122594","article-title":"Soluplus\u00ae promotes efficient transport of meloxicam to the central nervous system via nasal administration","volume":"632","author":"Sipos","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_28","unstructured":"ICH (2009). Pharmaceutical Development Q8; ICH Harmonised Tripartite Guideline, ICH."},{"key":"ref_29","unstructured":"ICH (2005). Quality Risk Management Q9; ICH Harmonised Tripartite Guideline, ICH."},{"key":"ref_30","unstructured":"ICH (2008). ICH Q10 Pharmaceutical Quality Systems, ICH."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sipos, B., Szab\u00f3-R\u00e9v\u00e9sz, P., Cs\u00f3ka, I., Pallagi, E., Dob\u00f3, D.G., B\u00e9lteky, P., K\u00f3nya, Z., De\u00e1k, \u00c1., Janov\u00e1k, L., and Katona, G. (2020). Quality by Design based formulation study of meloxicam-loaded polymeric micelles for intranasal administration. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080697"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1021\/acs.macromol.6b01371","article-title":"LCST behavior of symmetrical PNiPAm-b-PEtOx-bPNiPAm triblock copolymers","volume":"49","author":"Martin","year":"2016","journal-title":"Macromol"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1039\/c2py20309j","article-title":"Poly(tris(hydroxymethyl)acrylamidomethane)-based copolymers: A new class of acid-labile thermosensitive polymers","volume":"9","author":"Monge","year":"2012","journal-title":"Pol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1039\/C3PY00971H","article-title":"Dual pH- and temperature-responsive RAFT-based block co-polymer micelles and polymer\u2013protein conjugates with transient solubility","volume":"5","author":"Zhang","year":"2014","journal-title":"Pol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sipos, B., Katona, G., Szarvas, F.M., Budai-Sz\u0171cs, M., Ambrus, R., and Cs\u00f3ka, I. (2023). Development of vinpocetine-loaded nasal polymeric micelles via nano-spray-drying. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101447"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.jconrel.2021.02.031","article-title":"Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions","volume":"332","author":"Ghezzi","year":"2021","journal-title":"JCR"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kancharla, S., Zoyhofski, N.A., Bufalini, L., Chatelais, B.F., and Alexandridis, P. (2020). Association between Nonionic Amphiphilic Polymer and Ionic Surfactant in Aqueous Solutions: Effect of Polymer Hydrophobicity and Micellization. Polymers, 12.","DOI":"10.3390\/polym12081831"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jcis.2020.11.022","article-title":"Self-assembly and viscosity changes of binary surfactant solutions: A molecular dynamics study","volume":"585","author":"Zhou","year":"2021","journal-title":"J. Coll. Interface Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.1016\/j.vaccine.2007.03.038","article-title":"Pluronic\u00ae F127 enhances the effect as an adjuvant of chitosan microspheres in the intranasal delivery of Bordetella bronchiseptica antigens containing dermonecrotoxin","volume":"25","author":"Kang","year":"2007","journal-title":"Vaccine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ijpharm.2019.01.030","article-title":"Updates on thermosensitive hydrogel for nasal, ocular and cutaneous delivery","volume":"559","author":"Wang","year":"2019","journal-title":"Int. J. Pharm."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/6\/703\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:47:47Z","timestamp":1760107667000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/6\/703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,24]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["pharmaceutics16060703"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16060703","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,24]]}}}