title: In vitro evaluation of permeation, toxicity and effect of praziquantel-loaded solid lipid nanoparticles against Schistosoma mansoni as a strategy to improve efficacy of the schistosomiasis treatment.
abstract: Solid lipid nanoparticles (SLN) are a promising drug delivery system for oral administration of poorly-water soluble drugs because of their capacity to increase the solubility of drug molecules when loaded in their lipid matrices, with the resulting improvement of the drug bioavailability. In the present work, we have developed praziquantel (PZQ)-loaded SLN and explored the biological applications of this system for intestinal permeation of PZQ. The effect in vitro on Schistosoma mansoni culture and the cytotoxicity in HepG2 line cell were also evaluated. The results showed a significant decrease in the intestinal absorption of PZQ loaded in SLN compared to free PZQ, suggesting that the SLN matrix could act as reservoir system. In culture of S. mansoni, we observed that PZQ-loaded SLN were more effective than free PZQ, leading the death of the parasites in less time. The result was proportional to doses of PZQ (25 and 50 μg mL⁻¹) and lipid concentration. Regarding cytotoxicity, the encapsulation of PZQ into SLN decreased the toxicity in HepG2 cells in comparison to the free PZQ. From the obtained results, PZQ-loaded SLN could be a new drug delivery system for the schistosomiasis treatment especially in marginalized communities, improving the therapeutic efficacy and reducing the toxic effects of PZQ.
authors.affiliation: School of Pharmaceutical Sciences, UNESP - University Estadual Paulista, Rodovia Araraquara-Jau Km 1, Araraquara, SP 14801-902, Brazil; Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), P.O. Box 1013, 5001-801 Vila Real, Portugal.
authors.forename: Ana Luiza Ribeiro
authors.initials: AL
authors.lastname: de Souza
authors.affiliation: Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), P.O. Box 1013, 5001-801 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB/UTAD), Vila Real, Portugal.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Andreani
authors.affiliation: Institute of Biology, Department of Animal Biology, Laboratory of Helminthology, State University of Campinas, Rua Monteiro Lobato 255, CEP. 13083-862, Campinas, SP, Brazil.
authors.forename: Rosimeire Nunes
authors.initials: RN
authors.lastname: de Oliveira
authors.affiliation: School of Pharmaceutical Sciences, UNESP - University Estadual Paulista, Rodovia Araraquara-Jau Km 1, Araraquara, SP 14801-902, Brazil.
authors.forename: Charlene Priscila
authors.initials: CP
authors.lastname: Kiill
authors.affiliation: School of Pharmaceutical Sciences, UNESP - University Estadual Paulista, Rodovia Araraquara-Jau Km 1, Araraquara, SP 14801-902, Brazil.
authors.forename: Fernanda Kolenyak
authors.initials: FK
authors.lastname: dos Santos
authors.affiliation: Institute of Biology, Department of Animal Biology, Laboratory of Helminthology, State University of Campinas, Rua Monteiro Lobato 255, CEP. 13083-862, Campinas, SP, Brazil.
authors.forename: Silmara Marques
authors.initials: SM
authors.lastname: Allegretti
authors.affiliation: Department of Pharmacy, College of Pharmaceutical, Sorocaba University - UNISO, 18023-000 Sorocaba, SP, Brazil.
authors.forename: Marco Vinícius
authors.initials: MV
authors.lastname: Chaud
authors.affiliation: Faculty of Health Sciences, Department of Pharmaceutical Technology, Fernando Pessoa University, UFP, Rua Carlos da Maia 296, Office S.1, P-4200-150 Porto, Portugal; Institute of Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes e Alto Douro (IBB-CGB/UTAD), Vila Real, Portugal. Electronic address: eliana@ufp.edu.pt.
authors.forename: Eliana B
authors.initials: EB
authors.lastname: Souto
authors.affiliation: Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), P.O. Box 1013, 5001-801 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB/UTAD), Vila Real, Portugal.
authors.forename: Amélia M
authors.initials: AM
authors.lastname: Silva
authors.affiliation: School of Pharmaceutical Sciences, UNESP - University Estadual Paulista, Rodovia Araraquara-Jau Km 1, Araraquara, SP 14801-902, Brazil. Electronic address: pgremiao@fcfar.unesp.br.
authors.forename: Maria Palmira Daflon
authors.initials: MP
authors.lastname: Gremião
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011223:Praziquantel / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D012550:Schistosoma mansoni / Q000187:drug effects*; D012552:Schistosomiasis / Q000188:drug therapy
chemical_list: D000871:Anthelmintics; D003692:Delayed-Action Preparations; D008055:Lipids; D011223:Praziquantel
keywords: Cytotoxicity; HepG2 cells; Praziquantel; Schistosoma mansoni; Schistosomiasis; Solid lipid nanoparticles