{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:57:06Z","timestamp":1781567826702,"version":"3.54.5"},"reference-count":71,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Nacional de Rosario","award":["125\/2021"],"award-info":[{"award-number":["125\/2021"]}]},{"name":"Universidad Nacional de Rosario","award":["IO-2017-00220"],"award-info":[{"award-number":["IO-2017-00220"]}]},{"name":"Secretar\u00eda de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n de la Provincia de Santa Fe","award":["125\/2021"],"award-info":[{"award-number":["125\/2021"]}]},{"name":"Secretar\u00eda de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n de la Provincia de Santa Fe","award":["IO-2017-00220"],"award-info":[{"award-number":["IO-2017-00220"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>This study aimed to analyze whether the enhancement of the biopharmaceutical efficiency of mebendazole, a poorly water-soluble anthelmintic drug, significantly improves its antiparasitic activity in a murine model of trichinellosis. Objectives: Two advanced oral formulations were developed, polyvinyl alcohol-derived nanoparticles (NP) and \u03b2-cyclodextrin citrate inclusion complexes (Comp), both employing mebendazole as an anthelmintic agent. The primary objective of this work is to treat trichinellosis, an infection with severe chronic effects. Methods: The physicochemical characteristics as well as the in vivo performance of the NP and Comp formulations were assessed. The in vivo studies involved the bioavailability analysis, comparing drug absorption between the pure drug and the novel formulations, as well as the in vitro anthelmintic activity and in vivo therapeutic efficacy against Trichinella spiralis encysted muscle larvae. The in vivo efficacy was evaluated during the parenteral stage of T. spiralis infection in male and female mice from two genetically distinct lines differing in mebendazole pharmacokinetic parameters and susceptibility to the parasite. Results: The formulations exhibited smaller particle sizes and improved dissolution properties compared to pure MBZ. The pharmacokinetics studies indicate that NP and Comp significantly improved MBZ bioavailability. Both NP and Comp significantly increased mebendazole\u2019s anthelmintic activity against the encysted parasites, which would be attributed to the improved MBZ absorption. The formulations overcome the drug\u2019s poor solubility and low bioavailability limitations, resulting in a higher plasma concentration of the active drug, even at low doses. Conclusions: These findings suggest that the newly designed mebendazole formulations are suitable for treating T. spiralis chronic infection and highlight a potential improvement in the pharmacological treatment of trichinellosis.<\/jats:p>","DOI":"10.3390\/pharmaceutics17081069","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:59:01Z","timestamp":1755601141000},"page":"1069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Significant Improvement in Bioavailability and Therapeutic Efficacy of Mebendazole Oral Nano-Systems Assessed in a Murine Model with Extreme Phenotypes of Susceptibility to Trichinella spiralis"],"prefix":"10.3390","volume":"17","author":[{"given":"Ana V.","family":"Codina","sequence":"first","affiliation":[{"name":"Instituto de Gen\u00e9tica Experimental, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario S2000KTR, Argentina"},{"name":"Carrera del Investigador Cient\u00edfico de la Universidad Nacional de Rosario (CIC-UNR), Universidad Nacional de Rosario, Maip\u00fa 1065, Rosario S2000CGK, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Indelman","sequence":"additional","affiliation":[{"name":"\u00c1rea Parasitolog\u00eda, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas, Universidad Nacional de Rosario, Suipacha 531, Rosario S2002LRK, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7210-3215","authenticated-orcid":false,"given":"Lucila I.","family":"Hinrichsen","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Experimental, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario S2000KTR, Argentina"},{"name":"Carrera del Investigador Cient\u00edfico de la Universidad Nacional de Rosario (CIC-UNR), Universidad Nacional de Rosario, Maip\u00fa 1065, Rosario S2000CGK, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6738-1918","authenticated-orcid":false,"given":"Mar\u00eda C.","family":"Lamas","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica Rosario-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (IQUIR-CONICET), Suipacha 570, Rosario S2002LRK, Argentina"},{"name":"Departamento de Farmacia, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas, Universidad Nacional de Rosario, Suipacha 570, Rosario S2002LRK, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.fm.2016.12.012","article-title":"Meat Sources of Infection for Outbreaks of Human Trichinellosis","volume":"64","author":"Rostami","year":"2017","journal-title":"Food Microbiol."},{"key":"ref_2","unstructured":"Ryan, E.T., Hill, D.R., Solomon, T., Aronson, N.E., and Endy, T.P. 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