{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:50:22Z","timestamp":1776559822153,"version":"3.51.2"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014064","name":"Universidad de Salamanca","doi-asserted-by":"publisher","award":["KP3"],"award-info":[{"award-number":["KP3"]}],"id":[{"id":"10.13039\/501100014064","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The lyoprotective effects of mannitol and lactose have been evaluated in the production of sildenafil citrate liposomes. Liposomes were prepared by mixing the components under ultrasonic agitation, followed by a transmembrane pH gradient for remote drug loading. Mannitol and lactose, as compared to sucrose and trehalose, were used as the stabilizing agents, and different freeze-drying cycles were assayed. The remaining moisture and the thermal characteristics of the lyophilized samples were analyzed. Size, entrapment efficiency, biocompatibility, and cell internalization of original and rehydrated liposomes were compared. The type of additive did not affect the biocompatibility or cell internalization, but did influence other liposome attributes, including the thermal characteristics and the remaining moisture of the lyophilized samples. A cut-off of 5% (w\/w) remaining moisture was an indicator of primary drying completion\u2014information useful for scaling up and transfer from laboratory to large-scale production. Lactose increased the glass transition temperature to over 70 \u00b0C, producing lyoprotective effects similar to those obtained with sucrose. Based on these results, formulations containing liposomes lyophilized with lactose meet the FDA\u2019s requirements and can be used as a biocompatible and biodegradable vehicle for the pulmonary delivery of therapeutic doses of sildenafil citrate.<\/jats:p>","DOI":"10.3390\/pharmaceutics13081164","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T11:12:52Z","timestamp":1627470772000},"page":"1164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Lyoprotective Effects of Mannitol and Lactose Compared to Sucrose and Trehalose: Sildenafil Citrate Liposomes as a Case Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Mar\u00eda Jos\u00e9","family":"de Jes\u00fas Valle","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of the University of Salamanca (IBSAL), 37007 Salamanca, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0351-1757","authenticated-orcid":false,"given":"Andre\u00eda","family":"Alves","sequence":"additional","affiliation":[{"name":"CPIRN-IPG\u2014Center of Potential and Innovation of Natural Resources, Polytechnic Institute of Guarda, 6300-559 Guarda, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6832-3082","authenticated-orcid":false,"given":"Paula","family":"Coutinho","sequence":"additional","affiliation":[{"name":"CPIRN-IPG\u2014Center of Potential and Innovation of Natural Resources, Polytechnic Institute of Guarda, 6300-559 Guarda, Portugal"},{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilha, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-8115","authenticated-orcid":false,"given":"Maximiano","family":"Prata Ribeiro","sequence":"additional","affiliation":[{"name":"CPIRN-IPG\u2014Center of Potential and Innovation of Natural Resources, Polytechnic Institute of Guarda, 6300-559 Guarda, Portugal"},{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilha, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-0989","authenticated-orcid":false,"given":"Cristina","family":"Maderuelo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Salamanca, 37007 Salamanca, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4291-1035","authenticated-orcid":false,"given":"Amparo","family":"S\u00e1nchez Navarro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of the University of Salamanca (IBSAL), 37007 Salamanca, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5173(98)00398-6","article-title":"Pulmonary distribution and clearance of two beclomethasone liposome formulations in healthy volunteers","volume":"181","author":"Saari","year":"1999","journal-title":"Int. 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