Articles producció científica> Ciències Mèdiques Bàsiques

Oral Particle Uptake and Organ Targeting Drives the Activity of Amphotericin B Nanoparticles

  • Identification data

    Identifier: imarina:2188946
    Authors:
    Serrano, Dolores R.Lalatsa, AikateriniAuxiliadora Dea-Ayuela, M.Bilbao-Ramos, Pablo E.Garrett, Natalie L.Moger, JulianGuarro, JosepCapilla, JavierPaloma Ballesteros, M.Schaetzlein, Andreas G.Bolas, FranciscoTorrado, Juan J.Uchegbu, Ijeoma F.
    Abstract:
    There are very few drug delivery systems that target key organs via the oral route, as oral delivery advances normally address gastrointestinal drug dissolution, permeation, and stability. Here we introduce a nanomedicine in which nanoparticles, while also protecting the drug from gastric degradation, are taken up by the gastrointestinal epithelia and transported to the lung, liver, and spleen, thus selectively enhancing drug bioavailability in these target organs and diminishing kidney exposure (relevant to nephrotoxic drugs). Our work demonstrates, for the first time, that oral particle uptake and translocation to specific organs may be used to achieve a beneficial therapeutic response. We have illustrated this using amphotericin B, a nephrotoxic drug encapsulated within N-palmitoyl-N-methyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycol chitosan (GCPQ) nanoparticles, and have evidenced our approach in three separate disease states (visceral leishmaniasis, candidiasis, and aspergillosis) using industry standard models of the disease in small animals. The oral bioavailability of AmB-GCPQ nanoparticles is 24%. In all disease models, AmB-GCPQ nanoparticles show comparable efficacy to parenteral liposomal AmB (AmBisome). Our work thus paves the way for others to use nanoparticles to achieve a specific targeted delivery of drug to key organs via the oral route. This is especially important for drugs with a narrow therapeutic index.
  • Others:

    Author, as appears in the article.: Serrano, Dolores R.; Lalatsa, Aikaterini; Auxiliadora Dea-Ayuela, M.; Bilbao-Ramos, Pablo E.; Garrett, Natalie L.; Moger, Julian; Guarro, Josep; Capilla, Javier; Paloma Ballesteros, M.; Schaetzlein, Andreas G.; Bolas, Francisco; Torrado, Juan J.; Uchegbu, Ijeoma F.;
    Department: Ciències Mèdiques Bàsiques
    URV's Author/s: Capilla Luque, Javier / Guarro Artigas, Josep
    Keywords: Toxicity Tissue Palmitoyl glycol chitosan Oral delivery Nanoparticles Nanomedicine N-palmitoyl,n-methyl-n,n-dimethyl-n,n,n-trimethyl-6-o-glycol chitosan N -palmitoyl, n -methyl- n, n -dimethyl- n, n, n -trimethyl-6- o -glycol chitosan Formulations Drugs Delivery Brain Biodistribution Amphotericin b Advantages Absorption nanoparticles nanomedicine n-palmitoyl,n-methyl-n,n-dimethyl-n,n,n-trimethyl-6-o-glycol chitosan amphotericin b
    Abstract: There are very few drug delivery systems that target key organs via the oral route, as oral delivery advances normally address gastrointestinal drug dissolution, permeation, and stability. Here we introduce a nanomedicine in which nanoparticles, while also protecting the drug from gastric degradation, are taken up by the gastrointestinal epithelia and transported to the lung, liver, and spleen, thus selectively enhancing drug bioavailability in these target organs and diminishing kidney exposure (relevant to nephrotoxic drugs). Our work demonstrates, for the first time, that oral particle uptake and translocation to specific organs may be used to achieve a beneficial therapeutic response. We have illustrated this using amphotericin B, a nephrotoxic drug encapsulated within N-palmitoyl-N-methyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycol chitosan (GCPQ) nanoparticles, and have evidenced our approach in three separate disease states (visceral leishmaniasis, candidiasis, and aspergillosis) using industry standard models of the disease in small animals. The oral bioavailability of AmB-GCPQ nanoparticles is 24%. In all disease models, AmB-GCPQ nanoparticles show comparable efficacy to parenteral liposomal AmB (AmBisome). Our work thus paves the way for others to use nanoparticles to achieve a specific targeted delivery of drug to key organs via the oral route. This is especially important for drugs with a narrow therapeutic index.
    Thematic Areas: Química Pharmacology & pharmacy Pharmaceutical science Odontología Molecular medicine Medicine, research & experimental Medicina veterinaria Medicina ii Interdisciplinar Farmacia Engenharias iv Engenharias ii Drug discovery Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciência de alimentos Biotecnología Astronomia / física
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 15438384
    Author's mail: javier.capilla@urv.cat
    Author identifier: 0000-0002-0765-6403
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/acceptedVersion
    Link to the original source: https://pubs.acs.org/doi/10.1021/mp500527x
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Molecular Pharmaceutics. 12 (2): 420-431
    APA: Serrano, Dolores R.; Lalatsa, Aikaterini; Auxiliadora Dea-Ayuela, M.; Bilbao-Ramos, Pablo E.; Garrett, Natalie L.; Moger, Julian; Guarro, Josep; Capil (2015). Oral Particle Uptake and Organ Targeting Drives the Activity of Amphotericin B Nanoparticles. Molecular Pharmaceutics, 12(2), 420-431. DOI: 10.1021/mp500527x
    Article's DOI: 10.1021/mp500527x
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2015
    Publication Type: Journal Publications
  • Keywords:

    Drug Discovery,Medicine, Research & Experimental,Molecular Medicine,Pharmaceutical Science,Pharmacology & Pharmacy
    Toxicity
    Tissue
    Palmitoyl glycol chitosan
    Oral delivery
    Nanoparticles
    Nanomedicine
    N-palmitoyl,n-methyl-n,n-dimethyl-n,n,n-trimethyl-6-o-glycol chitosan
    N -palmitoyl, n -methyl- n, n -dimethyl- n, n, n -trimethyl-6- o -glycol chitosan
    Formulations
    Drugs
    Delivery
    Brain
    Biodistribution
    Amphotericin b
    Advantages
    Absorption
    nanoparticles
    nanomedicine
    n-palmitoyl,n-methyl-n,n-dimethyl-n,n,n-trimethyl-6-o-glycol chitosan
    amphotericin b
    Química
    Pharmacology & pharmacy
    Pharmaceutical science
    Odontología
    Molecular medicine
    Medicine, research & experimental
    Medicina veterinaria
    Medicina ii
    Interdisciplinar
    Farmacia
    Engenharias iv
    Engenharias ii
    Drug discovery
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciência de alimentos
    Biotecnología
    Astronomia / física
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