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Res."],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Nevertheless, Rapa clinical application is still prevented by its unfavorable chemical-physical properties, limited oral bioavailability, and adverse effects related to non-specific biodistribution. In this paper, the design and production of a novel formulation of Rapa based on nano into micro (NiM) particles are detailed. To achieve it, Rapa-loaded nanoparticles were produced by nanoprecipitation of an amphiphilic pegylated poly-\u025b-caprolactone\/polyhydroxyethyl aspartamide graft copolymer. The obtained nanoparticles that showed a drug loading of 14.4 wt% (corresponding to an encapsulation efficiency of 82 wt%) did not interact with mucins and were able to release and protect Rapa from degradation in simulated lung and cell fluids. To allow their local administration to the lungs as a dry powder, particle engineering at micro-sized level was done by embedding nanoparticles into mannitol-based microparticles by spray drying. Obtained NiM particles had a mean diameter of about 2-\u00b5, spherical shape and had good potential to be delivered to the lungs by a breath-activated dry powder inhalers. Rheological and turbidity experiments showed that these NiM particles can dissolve in lung simulated fluid and deliver the Rapa-loaded pegylated nanoparticles, which can diffuse through the mucus layer.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s13346-021-01102-5","type":"journal-article","created":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T07:02:34Z","timestamp":1645254154000},"page":"1859-1872","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation"],"prefix":"10.1007","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-9559","authenticated-orcid":false,"given":"Emanuela Fabiola","family":"Craparo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-8101","authenticated-orcid":false,"given":"Salvatore Emanuele","family":"Drago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-0782","authenticated-orcid":false,"given":"Fabiana","family":"Quaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0850-9533","authenticated-orcid":false,"given":"Francesca","family":"Ungaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-6564","authenticated-orcid":false,"given":"Gennara","family":"Cavallaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,19]]},"reference":[{"key":"1102_CR1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1080\/15548627.2017.1389823","volume":"14","author":"AC Racanelli","year":"2018","unstructured":"Racanelli AC, Kikkers SA, Choi AMK, Cloonan SM. 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