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