Poloxamer 188-Coated Ammonium Methacrylate Copolymer Nanocarriers Enhance Loperamide Permeability across Pgp-Expressing Epithelia

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dc.catalogadorjwg
dc.contributor.authorCatalan Figueroa, Johanna
dc.contributor.authorGarcía Alcalde, Mauricio Andrés
dc.contributor.authorCayazzo Contreras, Pilar Andrea
dc.contributor.authorBoisset, Constanza B.
dc.contributor.authorGonzalez, Pablo M.
dc.contributor.authorFiedler, Jenny L.
dc.contributor.authorPerez, Mariela F.
dc.contributor.authorMorales, Javier O.
dc.date.accessioned2025-01-02T17:45:15Z
dc.date.available2025-01-02T17:45:15Z
dc.date.issued2021
dc.description.abstractLoperamide is a mu-opioid agonist with poor gastrointestinal absorption, mainly because of its modest aqueous solubility and being a P-glycoprotein (Pgp) efflux substrate. Nevertheless, studies associated with therapeutic effects strongly suggest that loperamide holds potential pharmacological advantages over traditional mu-opioid agonists commonly used for analgesia. Thus, in this Communication, we assessed in MDCK-hMDR1 cell lines the effects over loperamide uptake and efflux ratio, when loaded into Eudragit RS (ERS) nanocarriers coated with poloxamer 188 (P188). ERS was chosen for enhancing loperamide aqueous dispersibility and P188 as a potential negative Pgp modulator. In uptake assays, it was observed that Pgp limited the accumulation of loperamide into cells and that preincubation with P188, but not coincubation, led to increasing loperamide uptake at a similar extent of Pgp pharmacological inhibition. On the other hand, the efflux ratio displayed no alterations when Pgp was pharmacologically inhibited, whereas ERS/P188 nanocarriers effectively enhanced loperamide uptake and absorptive transepithelial transport. The latter suggests that loperamide transport across cells is significantly influenced by the presence of the unstirred water layer (UWL), which could hinder the visualization of Pgp-efflux effects during transport assays. Thus, results in this work highlight that formulating loperamide into this nanocarrier enhances its uptake and transport permeability.
dc.description.funderANID/FONDECYT Regular
dc.description.funderCONICYT
dc.format.extent8
dc.fuente.origenORCID
dc.identifier.doi10.1021/acs.molpharmaceut.0c00623
dc.identifier.eissn1543-8392
dc.identifier.issn1543-8384
dc.identifier.pubmedidMEDLINE:33044825
dc.identifier.urihttps://doi.org/10.1021/acs.molpharmaceut.0c00623
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89458
dc.identifier.wosidWOS:000641957900020
dc.information.autorucEscuela de Química; Garcia Alcalde Mauricio Andres; S/I; 181066
dc.information.autorucEscuela de Química; Cayazzo Contreras Pilar Andrea; S/I; 224420
dc.issue.numero2
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final750
dc.pagina.inicio743
dc.publisherAMER CHEMICAL SOC
dc.revistaMolecular Pharmaceutics
dc.rightsacceso restringido
dc.subjectAntibiotic resistance
dc.subjectMonolayers
dc.subjectNanocarriers
dc.subjectPeptides and proteins
dc.subjectPermeability
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titlePoloxamer 188-Coated Ammonium Methacrylate Copolymer Nanocarriers Enhance Loperamide Permeability across Pgp-Expressing Epithelia
dc.typeartículo
dc.volumen18
sipa.codpersvinculados181066
sipa.codpersvinculados224420
sipa.trazabilidadORCID;2024-12-23
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