{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:31Z","timestamp":1790017951593,"version":"4.0.1"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T00:00:00Z","timestamp":1685318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood\u2013brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a B\u00fcchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product.<\/jats:p>","DOI":"10.3390\/molecules28114406","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T03:39:36Z","timestamp":1685331576000},"page":"4406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development and Evaluation of an FDM Printed Nasal Device for CPZ Solid Nanoparticles"],"prefix":"10.3390","volume":"28","author":[{"given":"Thinh","family":"To Quoc","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"},{"name":"Institute of Healthcare Industry, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"B\u00edr\u00f3","sequence":"additional","affiliation":[{"name":"Doctoral School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"},{"name":"Hospital Pharmacy at the University of Debrecen, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gota","family":"Pet\u0151","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"},{"name":"Institute of Healthcare Industry, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra","family":"K\u00f3sa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"},{"name":"Institute of Healthcare Industry, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1vid","family":"Sinka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0992-4176","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Lekli","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3601-5143","authenticated-orcid":false,"given":"Attila","family":"Kiss-Szikszai","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, University of Debrecen, Egyetem t\u00e9r 1, 4010 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-3817","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Budai","sequence":"additional","affiliation":[{"name":"Department of Engineering Management and Enterprise, Institute of Industrial Process Management, Faculty of Engineering, University of Debrecen, \u00d3temet\u0151 utca 2, 4028 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8610-3788","authenticated-orcid":false,"given":"M\u00f3nika","family":"B\u00e9res","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Department of Radiology and Imaging Science, Faculty of General Medicine, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-975X","authenticated-orcid":false,"given":"Mikl\u00f3s","family":"Vecserny\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e1lma","family":"Feh\u00e9r","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8663-2890","authenticated-orcid":false,"given":"Ildik\u00f3","family":"B\u00e1cskay","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"},{"name":"Institute of Healthcare Industry, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9724-0614","authenticated-orcid":false,"given":"Zolt\u00e1n","family":"Ujhelyi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Pharmaceutical Sciences, University of 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(2008). Intranasal Delivery Bypasses the Blood-Brain Barrier to Target Therapeutic Agents to the Central Nervous System and Treat Neurodegenerative Disease. BMC Neurosci., 9.","DOI":"10.1186\/1471-2202-9-S3-S5"},{"key":"ref_2","unstructured":"Eleni, K., Paraskevi, P., and Georgia, V. (Vaccine, 2023). Advances in intranasal vaccine delivery: A promising non-invasive route of immunization, Vaccine, in press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.3390\/molecules14093754","article-title":"Nasal Delivery of High Molecular Weight Drugs","volume":"14","author":"Ozsoy","year":"2009","journal-title":"Molecules"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pires, P.C., Rodrigues, M., Alves, G., and Santos, A.O. (2022). Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030588"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1111\/j.1399-3038.2010.01015.x","article-title":"Compliance with Topical Nasal Medication\u2014An Evaluation in Children with Rhinitis","volume":"21","author":"Wong","year":"2010","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Musumeci, T., Bonaccorso, A., and Puglisi, G. (2019). Epilepsy Disease and Nose-to-Brain Delivery of Polymeric Nanoparticles: An Overview. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11030118"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1021\/jm00392a019","article-title":"Charged Analogs of Chlorpromazine as Dopamine Antagonists","volume":"30","author":"Harrold","year":"1987","journal-title":"J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106008","DOI":"10.1016\/j.bioorg.2022.106008","article-title":"Novel chlorpromazine derivatives as anti-endometrial carcinoma agents with reduced extrapyramidal side effects","volume":"127","author":"Li","year":"2022","journal-title":"Bioorganic Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.5694\/j.1326-5377.1960.tb105307.x","article-title":"Progressive chlorpromazine jaundice during pregnancy","volume":"1","author":"Mackay","year":"1960","journal-title":"Med. J. Aust."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Najahi-Missaoui, W., Arnold, R.D., and Cummings, B.S. (2020). Safe Nanoparticles: Are We There Yet?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010385"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/CCO.0000000000000828","article-title":"Nanoparticle Therapy for Head and Neck Cancers","volume":"34","author":"Hoffmann","year":"2022","journal-title":"Curr. Opin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1021\/bm049200j","article-title":"Novel Functionalized Biodegradable Polymers for Nanoparticle Drug Delivery Systems","volume":"6","author":"Kallinteri","year":"2005","journal-title":"Biomacromolecules"},{"key":"ref_13","first-page":"149","article-title":"Surface-Active Agents","volume":"18","author":"LESLIE","year":"1947","journal-title":"Manuf. Chem. Aerosol News"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/j.jaad.2020.07.057","article-title":"Hand Hygiene during COVID-19: Recommendations from the American Contact Dermatitis Society","volume":"83","author":"Rundle","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6459","DOI":"10.2174\/0929867326666190827151741","article-title":"Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery","volume":"26","author":"Alshweiat","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sibinovska, N., \u017dakelj, S., Trontelj, J., and Kristan, K. (2022). Applicability of RPMI 2650 and Calu-3 Cell Models for Evaluation of Nasal Formulations. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020369"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s43094-022-00400-0","article-title":"Pharmaceutical Nanotechnology: From the Bench to the Market","volume":"8","author":"Mazayen","year":"2022","journal-title":"Futur. J. Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.17219\/pim\/152230","article-title":"Spray Drying and Nano Spray Drying as Manufacturing Methods of Drug-Loaded Polymeric Particles","volume":"52","author":"Strojewski","year":"2022","journal-title":"Polym. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.2147\/DDDT.S66654","article-title":"Nanoparticle formulation by B\u00fcchi B-90 Nano Spray Dryer for oral mucoadhesion","volume":"9","author":"Harsha","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s12011-019-01730-6","article-title":"Selenium Overcomes Doxorubicin Resistance in Their Nano-Platforms Against Breast and Colon Cancers","volume":"193","author":"Ahmed","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2B.2.1","DOI":"10.1002\/9780471729259.mc02b02s25","article-title":"Scanning Electron Microscopy","volume":"25","author":"Fischer","year":"2012","journal-title":"Curr. Protoc. Microbiol."},{"key":"ref_22","unstructured":"Marx, D., Williams, G., and Birkhoff, M. (2015). Drug Discovery and Development\u2014From Molecules to Medicine, InTech."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Harish, V., Ansari, M.M., Tewari, D., Gaur, M., Yadav, A.B., Garc\u00eda-Betancourt, M.-L., Abdel-Haleem, F.M., Bechelany, M., and Barhoum, A. (2022). Nanoparticle and Nanostructure Synthesis and Controlled Growth Methods. Nanomaterials, 12.","DOI":"10.3390\/nano12183226"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5313","DOI":"10.2174\/1381612822666160720163656","article-title":"Strategies That Target Tight Junctions for Enhanced Drug Delivery","volume":"22","author":"Posadas","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1111\/j.2042-7158.2012.01540.x","article-title":"Cultivation of RPMI 2650 Cells as an In-Vitro Model for Human Transmucosal Nasal Drug Absorption Studies: Optimization of Selected Culture Conditions","volume":"64","author":"Reichl","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1365-2818.2011.03513.x","article-title":"Quantitative Micro-CT","volume":"243","author":"SCHLADITZ","year":"2011","journal-title":"J. Microsc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105","DOI":"10.17795\/jjnpp-9373","article-title":"Preparation and Characterization of Dexamethasone Microemulsion Based on Pseudoternary Phase Diagram","volume":"8","author":"Moghimipour","year":"2013","journal-title":"Jundishapur J. Nat. Pharm. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1208\/s12249-021-02001-1","article-title":"Development and Characterization of Excipient Enhanced Growth (EEG) Surfactant Powder Formulations for Treating Neonatal Respiratory Distress Syndrome","volume":"22","author":"Boc","year":"2021","journal-title":"AAPS Pharm. Sci. Tech."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1021\/nn7000799","article-title":"Scanning Electron Microscopy of Nanoscale Chemical Patterns","volume":"1","author":"Srinivasan","year":"2007","journal-title":"ACS Nano"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1248\/yakushi.18-00171-1","article-title":"Nanosize Particle Analysis by Dynamic Light Scattering (DLS)","volume":"139","author":"Ashizawa","year":"2019","journal-title":"Yakugaku Zasshi"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.culher.2017.02.010","article-title":"3D Printing: State of the Art and Future Perspectives","volume":"26","author":"Balletti","year":"2017","journal-title":"J. Cult. Herit."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ejpb.2019.10.008","article-title":"Suitability of RPMI 2650 Cell Models for Nasal Drug Permeability Prediction","volume":"145","author":"Sibinovska","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.jab.2016.06.001","article-title":"Investigation of Betahistine Dihydrochloride Biocompatibility and Nasal Permeability In Vitro","volume":"14","author":"Pilicheva","year":"2016","journal-title":"J. Appl. Biomed."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/11\/4406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:44:04Z","timestamp":1760125444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/11\/4406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,29]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["molecules28114406"],"URL":"https:\/\/doi.org\/10.3390\/molecules28114406","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,29]]}}}