Serrano, DR;
Lalatsa, A;
Dea-Ayuela, MA;
Bilbao-Ramos, PE;
Garrett, NL;
Moger, J;
Guarro, J;
... Uchegbu, IF; + view all
(2015)
Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles.
Molecular Pharmaceutics
, 12
(2)
pp. 420-431.
10.1021/mp500527x.
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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.
| Type: | Article |
|---|---|
| Title: | Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/mp500527x |
| Publisher version: | http://dx.doi.org/10.1021/mp500527x |
| Language: | English |
| Additional information: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: http://dx.doi.org/10.1021/mp500527x. |
| Keywords: | N-palmitoyl,N-methyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycol chitosan, amphotericin B, nanomedicine, nanoparticles, oral delivery, Administration, Oral, Amphotericin B, Animals, Antifungal Agents, Antiprotozoal Agents, Drug Delivery Systems, Drug Stability, Male, Mice, Mice, Inbred BALB C, Nanomedicine, Nanoparticles |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1460699 |
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