Oral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles.

2.50
Hdl Handle:
http://hdl.handle.net/2436/618247
Title:
Oral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles.
Authors:
Huarte, Judit; Espuelas, Socorro; Lai, Yusi; He, Bin; Tang, James Z; Irache, Juan M
Abstract:
Camptothecin (CPT), a molecule that shows powerful anticancer activity, is still not used in clinic due to its high hydrophobicity and poor active form's stability. In order to solve these drawbacks, the combination between poly(anhydride) nanoparticles and cyclodextrins was evaluated. CPT-loaded nanoparticles, prepared in the presence of 2-hydroxypropyl-β-cyclodextrin, (HPCD-NP) displayed a mean size close to 170nm and a payload of 50μg per mg (25 times higher than the one of the control nanoparticles). CPT was not released from nanoparticles under gastric conditions. However, under intestinal conditions, about 50% of the drug content was released as a burst, whereas the remained drug was released following a zero-order kinetic. Pharmacokinetic studies revealed that the CPT plasma levels, from orally administered nanoparticles, were high and sustained up to 48h. The CPT oral bioavailability was 7-fold higher than the value obtained with the control, whereas its clearance was significantly lower than for the aqueous suspension. These observations may be directly related to a prolonged residence time of nanoparticles in close contact with the intestinal epithelium, the presence of the cyclodextrin that decreases the CPT transformation into its inactive form and the generation of an acidic microenvironment during the degradation of the poly(anhydride) that would prevent the transformation of the active lactone into the inactive carboxylate conformation.
Citation:
Oral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles. 2016, 506 (1-2):116-28 Int J Pharm
Publisher:
Elsevier
Journal:
International journal of pharmaceutics
Issue Date:
15-Jun-2016
URI:
http://hdl.handle.net/2436/618247
DOI:
10.1016/j.ijpharm.2016.04.045
PubMed ID:
27102993
Type:
Article
Language:
en
ISSN:
0378-5173
Appears in Collections:
FSE

Full metadata record

DC FieldValue Language
dc.contributor.authorHuarte, Juditen
dc.contributor.authorEspuelas, Socorroen
dc.contributor.authorLai, Yusien
dc.contributor.authorHe, Binen
dc.contributor.authorTang, James Zen
dc.contributor.authorIrache, Juan Men
dc.date.accessioned2016-08-11T13:26:56Z-
dc.date.available2016-08-11T13:26:56Z-
dc.date.issued2016-06-15-
dc.identifier.citationOral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles. 2016, 506 (1-2):116-28 Int J Pharmen
dc.identifier.issn0378-5173en
dc.identifier.pmid27102993-
dc.identifier.doi10.1016/j.ijpharm.2016.04.045-
dc.identifier.urihttp://hdl.handle.net/2436/618247-
dc.description.abstractCamptothecin (CPT), a molecule that shows powerful anticancer activity, is still not used in clinic due to its high hydrophobicity and poor active form's stability. In order to solve these drawbacks, the combination between poly(anhydride) nanoparticles and cyclodextrins was evaluated. CPT-loaded nanoparticles, prepared in the presence of 2-hydroxypropyl-β-cyclodextrin, (HPCD-NP) displayed a mean size close to 170nm and a payload of 50μg per mg (25 times higher than the one of the control nanoparticles). CPT was not released from nanoparticles under gastric conditions. However, under intestinal conditions, about 50% of the drug content was released as a burst, whereas the remained drug was released following a zero-order kinetic. Pharmacokinetic studies revealed that the CPT plasma levels, from orally administered nanoparticles, were high and sustained up to 48h. The CPT oral bioavailability was 7-fold higher than the value obtained with the control, whereas its clearance was significantly lower than for the aqueous suspension. These observations may be directly related to a prolonged residence time of nanoparticles in close contact with the intestinal epithelium, the presence of the cyclodextrin that decreases the CPT transformation into its inactive form and the generation of an acidic microenvironment during the degradation of the poly(anhydride) that would prevent the transformation of the active lactone into the inactive carboxylate conformation.en
dc.language.isoenen
dc.publisherElsevieren
dc.rightsArchived with thanks to International journal of pharmaceuticsen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCamptothecinen
dc.subjectNanoparticlesen
dc.subjectCyclodextrinsen
dc.subjectOral deliveryen
dc.titleOral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles.en
dc.typeArticleen
dc.identifier.journalInternational journal of pharmaceuticsen
dc.date.accepted2016-04-16-
rioxxterms.funderHEPTAG EXCHANGEen
rioxxterms.identifier.projectFP7-MC-IRSES-2011 (2012-2015)en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2017-04-19en

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.