{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:13Z","timestamp":1790017933511,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,4]],"date-time":"2023-03-04T00:00:00Z","timestamp":1677888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lembaga Pengelola Dana Pendidikan\/LPDP","award":["SBF005\\1011"],"award-info":[{"award-number":["SBF005\\1011"]}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["SBF005\\1011"],"award-info":[{"award-number":["SBF005\\1011"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75\/25 D,L-Lactide\/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT\/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I\u2212 took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants.<\/jats:p>","DOI":"10.3390\/pharmaceutics15030843","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T06:29:06Z","timestamp":1678084146000},"page":"843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Radiolabeled Risperidone microSPECT\/CT Imaging for Intranasal Implant Studies Development"],"prefix":"10.3390","volume":"15","author":[{"given":"Jon Ander","family":"Sim\u00f3n","sequence":"first","affiliation":[{"name":"Radiopharmacy Unit, Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, IdiSNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Utomo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix","family":"Pareja","sequence":"additional","affiliation":[{"name":"Radiopharmacy Unit, Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, IdiSNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1162-1470","authenticated-orcid":false,"given":"Mar\u00eda","family":"Collantes","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging Unit (UNIMTRA), Department of Nuclear Medicine, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Quincoces","sequence":"additional","affiliation":[{"name":"Radiopharmacy Unit, Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, IdiSNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aar\u00f3n","family":"Otero","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging Unit (UNIMTRA), Department of Nuclear Medicine, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Ecay","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging Unit (UNIMTRA), Department of Nuclear Medicine, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-8434","authenticated-orcid":false,"given":"Juan","family":"Dom\u00ednguez-Robles","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK"},{"name":"Department of Pharmacy and Pharmaceutical Technology, University of Seville, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3710-0438","authenticated-orcid":false,"given":"Eneko","family":"Larra\u00f1eta","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-976X","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Pe\u00f1uelas","sequence":"additional","affiliation":[{"name":"Radiopharmacy Unit, Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, IdiSNA, 31008 Pamplona, Spain"},{"name":"Translational Molecular Imaging Unit (UNIMTRA), Department of Nuclear Medicine, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ejpb.2020.12.005","article-title":"Evolution of drug-eluting biomedical implants for sustained drug delivery","volume":"159","author":"Quarterman","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Stewart, A.S., Dom\u00ednguez-Robles, J., Donnelly, R.F., and Larra\u00f1eta, E. (2018). Implantable polymeric drug delivery devices: Classification, manufacture, materials, and clinical applications. Polymers, 10.","DOI":"10.3390\/polym10121379"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41578-021-00405-w","article-title":"Clinical translation of long-acting drug delivery formulations","volume":"7","author":"Li","year":"2022","journal-title":"Nat. Rev. Mater."},{"key":"ref_4","unstructured":"Chappel, E. (2021). Drug Delivery Devices and Therapeutic Systems, Elsevier."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"213024","DOI":"10.1016\/j.bioadv.2022.213024","article-title":"3D-printed reservoir-type implants containing poly(lactic acid)\/poly(caprolactone) porous membranes for sustained drug delivery","volume":"139","author":"Korelidou","year":"2022","journal-title":"Biomater. Adv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1021\/acs.molpharmaceut.0c00515","article-title":"Poly(caprolactone)-based coatings on 3d-printed biodegradable implants: A novel strategy to prolong delivery of hydrophilic drugs","volume":"17","author":"Stewart","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_7","unstructured":"Kumar, A., and Pillai, J. (2018). Nanostructures for the Engineering of Cells, Tissues and Organs, Elsevier."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"113957","DOI":"10.1016\/j.addr.2021.113957","article-title":"Polymeric long-acting drug delivery systems (ladds) for treatment of chronic diseases: Inserts, patches, wafers, and implants","volume":"177","author":"Abdelkader","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"122477","DOI":"10.1016\/j.ijpharm.2022.122477","article-title":"Development of 3d-printed subcutaneous implants using concentrated polymer\/drug solutions","volume":"631","author":"Picco","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s11095-020-2777-2","article-title":"Design of a drug-eluting subcutaneous implant of the antiretroviral tenofovir alafenamide fumarate","volume":"37","author":"Simpson","year":"2020","journal-title":"Pharm. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"121011","DOI":"10.1016\/j.ijpharm.2021.121011","article-title":"Poly(caprolactone)-based subcutaneous implant for sustained delivery of levothyroxine","volume":"607","author":"Stewart","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_12","first-page":"100068","article-title":"A New Engineering process of biodegradable polymeric solid implants for ultra-long-acting drug delivery","volume":"3","author":"Maturavongsadit","year":"2021","journal-title":"Int. J. Pharm. X"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eabj4624","DOI":"10.1126\/sciadv.abj4624","article-title":"Implantable system for chronotherapy","volume":"7","author":"Lee","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.jconrel.2022.10.054","article-title":"User-designed device with programmable release profile for localized treatment","volume":"352","author":"Myung","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.15420\/ecr.2018:8:2","article-title":"de la The newest generation of drug-eluting stents and beyond","volume":"13","author":"Lee","year":"2018","journal-title":"Eur. Cardiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112375","DOI":"10.1016\/j.msec.2021.112375","article-title":"Development of drug loaded cardiovascular prosthesis for thrombosis prevention using 3D printing","volume":"129","author":"Shen","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1582-4934.2008.00532.x","article-title":"Drug releasing systems in cardiovascular tissue engineering","volume":"13","author":"Spadaccio","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121153","DOI":"10.1016\/j.ijpharm.2021.121153","article-title":"3D printing advances in the development of stents","volume":"609","author":"Khalaj","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5712594","DOI":"10.1155\/2019\/5712594","article-title":"Patient-specific coronary artery 3d printing based on intravascular optical coherence tomography and coronary angiography","volume":"2019","author":"Huang","year":"2019","journal-title":"Complexity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"275101","DOI":"10.1088\/1361-6528\/aabc69","article-title":"Dipyridamole-loaded biodegradable pla nanoplatforms as coatings for cardiovascular stents","volume":"29","author":"Bakola","year":"2018","journal-title":"Nanotechnology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120243","DOI":"10.1016\/j.ijpharm.2021.120243","article-title":"Fused deposition modelling for the development of drug loaded cardiovascular prosthesis","volume":"595","author":"Martin","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"0080","DOI":"10.1038\/s41551-017-0080","article-title":"A Fully functional drug-eluting joint implant","volume":"1","author":"Suhardi","year":"2017","journal-title":"Nat. Biomed. Eng."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ma, X., Gao, Y., Zhao, D., Zhang, W., Zhao, W., Wu, M., Cui, Y., Li, Q., Zhang, Z., and Ma, C. (2021). Titanium implants and local drug delivery systems become mutual promoters in orthopedic clinics. Nanomaterials, 12.","DOI":"10.3390\/nano12010047"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3390\/pharmaceutics6020249","article-title":"Drug-eluting nasal implants: Formulation, characterization, clinical applications and challenges","volume":"6","author":"Parikh","year":"2014","journal-title":"Pharmaceutics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s13346-020-00891-5","article-title":"Intranasal Drug Delivery: Opportunities and toxicologic challenges during drug development","volume":"12","author":"Keller","year":"2022","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"122061","DOI":"10.1016\/j.ijpharm.2022.122061","article-title":"Development of intranasal implantable devices for schizophrenia treatment","volume":"624","author":"Utomo","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101631","DOI":"10.1016\/j.apmt.2022.101631","article-title":"On a highway to the brain: A review on nose-to-brain drug delivery using nanoparticles","volume":"29","author":"Formica","year":"2022","journal-title":"Appl. Mater. Today"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Aderibigbe, B. (2018). In situ-based gels for nose to brain delivery for the treatment of neurological diseases. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020040"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jconrel.2020.07.044","article-title":"Stimuli-responsive in situ gelling system for nose-to-brain drug delivery","volume":"327","author":"Agrawal","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10967-014-3139-5","article-title":"Preparation and biological evaluation of radioiodinated risperidone and lamotrigine as models for brain imaging agents","volume":"301","author":"Saddar","year":"2014","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25223","DOI":"10.1039\/D0RA04943C","article-title":"A concise method for fully automated radiosyntheses of [ 18 F]jnj-46356479 and [ 18 F]fitm via cu-mediated 18 F-fluorination of organoboranes","volume":"10","author":"Yuan","year":"2020","journal-title":"RSC Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18161","DOI":"10.1038\/s41598-022-21687-2","article-title":"Performance evaluation of a preclinical SPECT\/CT system for multi-animal and multi-isotope quantitative experiments","volume":"12","author":"Prieto","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_33","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":"2011","journal-title":"J. Drug Target."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1080\/03639045.2019.1619759","article-title":"Formulation and biopharmaceutical evaluation of risperidone-loaded chitosan nanoparticles for intranasal delivery","volume":"45","author":"Rukmangathen","year":"2019","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/alr.22443","article-title":"Efficacy of steroid-eluting stents in management of chronic rhinosinusitis after endoscopic sinus surgery: Updated meta-analysis","volume":"9","author":"Goshtasbi","year":"2019","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1001\/jamaoto.2018.2944","article-title":"Use of corticosteroid-eluting sinus stents between 2012 and 2017","volume":"145","author":"Gadkaree","year":"2019","journal-title":"JAMA Otolaryngol. Neck Surg."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, C., Yu, L., Chu, X., Wang, K., Li, J., Lai, Y., Meng, C., Wen, W., Zhu, D., and Zhang, Y. (2022). Short-term postoperative efficacy of steroid-eluting stents for eosinophilic chronic rhinosinusitis with nasal polyps: A randomized clinical trial. Int. Forum Allergy Rhinol.","DOI":"10.1002\/alr.23085"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1177\/0145561320947632","article-title":"Comparison of bioabsorbable steroid-eluting sinus stents versus nasopore after endoscopic sinus surgery: A multicenter, randomized, controlled, single-blinded clinical trial","volume":"101","author":"Huang","year":"2022","journal-title":"Ear Nose Throat J."},{"key":"ref_40","unstructured":"Larra\u00f1eta, E., Raghu Raj Singh, T., and Donnelly, R.F. (2022). Long-Acting Drug Delivery Systems, Elsevier."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"120330","DOI":"10.1016\/j.ijpharm.2021.120330","article-title":"3D printed polymeric drug-eluting implants","volume":"597","author":"Liaskoni","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121435","DOI":"10.1016\/j.biomaterials.2022.121435","article-title":"Wearable and implantable devices for drug delivery: Applications and challenges","volume":"283","author":"Kar","year":"2022","journal-title":"Biomaterials"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10544-019-0389-6","article-title":"Advanced implantable drug delivery technologies: Transforming the clinical landscape of therapeutics for chronic diseases","volume":"21","author":"Ballerini","year":"2019","journal-title":"Biomed. Microdevices"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1177\/2045125312474019","article-title":"Medication adherence in schizophrenia: Factors influencing adherence and consequences of nonadherence, a systematic literature review","volume":"3","author":"Higashi","year":"2013","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2147\/PROM.S42735","article-title":"Nonadherence with antipsychotic medication in schizophrenia: Challenges and management strategies","volume":"5","author":"Haddad","year":"2014","journal-title":"Patient Relat. Outcome Meas."},{"key":"ref_46","first-page":"e12473","article-title":"Suicidal behavior and medication adherence in schizophrenic patients","volume":"13","author":"Warriach","year":"2021","journal-title":"Cureus"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13033-021-00464-0","article-title":"Lifetime relapse and its associated factors among people with schizophrenia spectrum disorders who are on follow up at comprehensive specialized hospitals in amhara region, ethiopia: A cross-sectional study","volume":"15","author":"Moges","year":"2021","journal-title":"Int. J. Ment. Health Syst."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.2147\/PPA.S322880","article-title":"Relapse and treatment adherence in patients with schizophrenia switching from paliperidone palmitate once-monthly to three-monthly formulation: A retrospective health claims database analysis","volume":"15","author":"Li","year":"2021","journal-title":"Patient Prefer. Adherence"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Miranda, J.J., D\u00edaz-Fern\u00e1ndez, S., and L\u00f3pez-Mu\u00f1oz, F. (2022). Effectiveness of more personalized, case-managed, and multicomponent treatment for patients with severe schizophrenia compared to the standard treatment: A ten-year follow-up. J. Pers. Med., 12.","DOI":"10.3390\/jpm12071101"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s40273-017-0515-3","article-title":"The cost of relapse in schizophrenia","volume":"35","author":"Pennington","year":"2017","journal-title":"Pharmacoeconomics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1192\/bjp.184.4.346","article-title":"Relapse in schizophrenia: Costs, clinical outcomes and quality of life","volume":"184","author":"Almond","year":"2004","journal-title":"Br. J. Psychiatry"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/3\/843\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:47:57Z","timestamp":1760122077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/3\/843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,4]]},"references-count":51,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["pharmaceutics15030843"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15030843","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,4]]}}}