{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T14:32:00Z","timestamp":1777127520512,"version":"3.51.4"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The latest advances in pharmaceutical technology are leading to the development of cutting edged approaches to produce what is now known as the \u201cHoly Grail\u201d of medicine\u2014nanopharmaceutics. Over the latest decade, the pharmaceutical industry has made important contributions to the scale up of these new products. To ensure their quality, efficacy, and safety for human use, clinical trials are mandatory. Yet, regulation regarding nanopharmaceuticals is still limited with a set of guidelines being recently released with respect to compliance with quality and safety. For the coming years, updates on regulatory issues about nanopharmaceuticals and their use in clinical settings are expected. The use of nanopharmaceuticals in clinical trials depends on the approval of the production methods and assurance of the quality of the final product by implementation and verification of the good manufacturing practices (GMP). This review addresses the available legislation on nanopharmaceuticals within the European Union (EU), the GMP that should be followed for their production, and the current challenges encountered in clinical trials of these new formulations. The singular properties of nanopharmaceuticals over their bulk counterparts are associated with their size, matrix composition, and surface properties. To understand their relevance, four main clinical trial guidelines, namely, for intravenous iron-based nanopharmaceuticals, liposomal-based nanopharmaceuticals, block copolymer micelle-based nanopharmaceuticals, and related to surface coating requirements, are described here.<\/jats:p>","DOI":"10.3390\/pharmaceutics12020146","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T11:45:30Z","timestamp":1581421530000},"page":"146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":123,"title":["Nanopharmaceutics: Part I\u2014Clinical Trials Legislation and Good Manufacturing Practices (GMP) of Nanotherapeutics in the EU"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-6017","authenticated-orcid":false,"given":"Eliana B.","family":"Souto","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy (FFUC), University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-9722","authenticated-orcid":false,"given":"Gabriela F.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy (FFUC), University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8502-8701","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Dias-Ferreira","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy (FFUC), University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2603-1377","authenticated-orcid":false,"given":"Aleksandra","family":"Zielinska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy (FFUC), University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}]},{"given":"F\u00e1tima","family":"Ventura","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7747-9107","authenticated-orcid":false,"given":"Alessandra","family":"Durazzo","sequence":"additional","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}]},{"given":"Massimo","family":"Lucarini","sequence":"additional","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}]},{"given":"Ettore","family":"Novellino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-3327","authenticated-orcid":false,"given":"Antonello","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vieira, R., Souto, S.B., Sanchez-Lopez, E., Machado, A.L., Severino, P., Jose, S., Santini, A., Fortuna, A., Garcia, M.L., and Silva, A.M. (2019). Sugar-Lowering Drugs for Type 2 Diabetes Mellitus and Metabolic Syndrome-Review of Classical and New Compounds: Part-I. Pharmaceuticals, 12.","DOI":"10.3390\/ph12040152"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vieira, R., Souto, S.B., Sanchez-Lopez, E., Machado, A.L., Severino, P., Jose, S., Santini, A., Silva, A.M., Fortuna, A., and Garcia, M.L. (2019). 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