Combined hydroxypropyl-β-cyclodextrin and poly(anhydride) nanoparticles improve the oral permeability of paclitaxel

Agüeros, Maite; Ruiz-Gatón, Luisa; Vauthier, Christine; Bouchemal, Kawthar; Espuelas, Socorro; Ponchel, Gilles; Irache, Juan M.

doi:10.1016/j.ejps.2009.09.010

Cited by 128 publications

(61 citation statements)

References 41 publications

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“…In order to minimise this drawback, one possible solution may be the incorporation of cyclodextrins as promoters of drug loading for the preparation of nanoparticles. The resulting cyclodextrin-PVM/MA nanoparticles have been proven effective to both develop intense bioadhesive interactions between the gut (Agüeros et al, 2009a) and to increase the drug loading of lipophilic drugs such as paclitaxel (Agüeros et al 2009b). …”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

Calvo

Lavandera

Agüeros

et al. 2011

Biomed Microdevices

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The aim was to study the ability of bioadhesive cyclodextrin-poly(anhydride) nanoparticles as carriers for the oral delivery of atovaquone (ATO). In order to increase the loading capacity of ATO by poly(anhydride) nanoparticles, the following oligosaccharides were assayed: 2-hydroxypropyl--cyclodextrin (HPCD), 2,6-di-O-methyl-β-cyclodextrin (DCMD), randomly methylated-β-cyclodextrin (RMCD) and sulfobuthyl ether-β-cyclodextrin (SBECD).Nanoparticles were obtained by desolvation after the incubation between the poly(anhydride) with the ATO-cyclodextrin complexes. For the pharmacokinetic studies, ATO formulations were administered orally in rats. Overall, ATO displayed a higher affinity for methylated cyclodextrins than for the other derivatives. However, for in vivo studies, both ATO-DMCD-NP and ATO-HPCD-NP were chosen. These nanoparticle formulations showed more adequate physicochemical properties in terms of size (< 260 nm), drug loading (17.8 and 16.9 g/mg, respectively) and yield (>75%). In vivo, nanoparticle formulations induced higher and more prolonged plasmatic levels of atovaquone than control suspensions of the drug in methylcellulose. Relative bioavailability of ATO when loaded in nanoparticles ranged from 52% (for ATO-HPCD NP) to 71% (for ATO-DMCD NP), whereas for the suspension control formulation the bioavailability was only about 30%. The encapsulation of atovaquone in cyclodextrinspoly(anhydride) nanoparticles seems to be an interesting strategy to improve the oral bioavailability of this lipophilic drug.

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Section: Introductionmentioning

confidence: 99%

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

Calvo

Lavandera

Agüeros

et al. 2011

Biomed Microdevices

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“…De tels niveaux prolongés du paclitaxel témoignent du contrôle de la libération qu'exercent les nanoparticules de poly (anhydride). Les nanoparticules utilisées assurent une certaine gastrorésistance ; elles ne libèrent pas leur contenu en milieu acide et permettent, au contraire, sa libération lente dans les milieux aqueux proches de la neutralité [27,28]. Particulièrement intéressant est le fait que les niveaux plasmatiques de paclitaxel obtenus avec les nanoparticules pégylées sont plus élevés que la concentration minimale considérée comme thérapeutique (environ 85 ng/ml [37]).…”

Section: Discussion Et Conclusionunclassified

“…La quantité de paclitaxel encapsulée dans les nanoparticules a été déterminée par chromatographie liquide à haute performance [28]. A cette fin, un appareil CLHP Agilent 1100 series (Waldbornn, Germany) muni d'un système de prélèvement automatique et d'un détecteur à barrette de diodes a été utilisé.…”

Section: Dosage Du Paclitaxelunclassified

Nanoparticules mucopénétrantes : véhicules pour l’administration orale du paclitaxel

Zabaleta

Calleja

Espuelas

et al. 2013

Annales Pharmaceutiques Françaises

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RésuméLe paclitaxel est un agent anticancéreux utilisé en solution pour perfusion intraveineuse dans le traitement de différents types de cancer. Dans les dernières années, de nombreuses stratégies ont été proposées pour le développement d'une formulation orale de cet anticancéreux. Toutefois, la faible solubilité aqueuse du paclitaxel et le fait qu'il soit un substrat de la pglycoprotéine intestinale et du complexe enzymatique cytochrome P450 compliquent énormément le problème. Dans ce travail, des nanoparticules pégylées avec des propriétés mucopénétrantes ont été développées pour acheminer le paclitaxel jusqu'à la surface des entérocytes. Des particules présentant une taille moyenne d'environ 180 nm et un contenu en paclitaxel proche de 15% ont été préparées. Une étude pharmacocinétique chez la souris a montré que les nanoparticules permettent d'obtenir des niveaux plasmatiques efficaces et soutenus du paclitaxel pendant 3 jours. Au total, la biodisponibilité relative orale du paclitaxel, encapsulé dans des nanoparticules pégylées avec du PEG 2000, est proche du 85%. Chez la souris, sur un modèle de tumeur sous-cutanée, ces mêmes nanoparticules administrées par voie orale, une fois tous les trois jours, ont permis d'obtenir une efficacité similaire à celle offerte par le médicament commercialisé administré par voie intraveineuse journellement pendant 9 jours. L'ensemble des résultats tend à démontrer que les nanoparticules développées sont capables de traverser la couche du mucus intestinal et d'atteindre, ainsi, la surface des entérocytes. Les molécules de PEG favorisent l'adhésion des particules à la surface des cellules, évitent la métabolisation du paclitaxel et accroissent son absorption. Mots-clés : nanoparticules, paclitaxel, orale, poly (éthylène glycol), libération contrôlée SummaryPaclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with muco-penetrating properties in order to conduct paclitaxel till the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol administered intravenously every day during 9 days. 3All of these results suggested ...

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“…[102] Permeability of paclitaxel was improved by formulating the inclusion complexes with 2-hydroxyproply-β-cyclodextrin and further encapsulating these into the poly(anhydride) nanoparticles and found about 500 times higher drug loading and about 12-fold higher permeability as compared to control formulation. [103] The permeability of cyclodextrins can be increased of water soluble drugs by direct action on mucosal membrane and the drug absorption and bioavailability also enhanced. [104,105] …”

Section: Permeability Enhancementmentioning

confidence: 99%

Untitled

Budhwar¹

2018

AJP

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Inclusion complexes have various applications in different fields of drug delivery and pharmaceutical industry due to their ability of complexation with guest molecules and enhancement of the physicochemical properties of guest molecules. Cyclodextrins and their derivatives have the ability to encapsulate the bioactive compounds into its cavity and protect these from the environmental conditions, improve the solubility, bioavailability, and other properties also. The aim of this review is to highlight the advantages of cyclodextrins in the enhancement of physicochemical properties of drugs (such as solubility, stability, bioavailability, permeability, and others), different methods for production and various characterization techniques used for evaluation of complexes. Applications of cyclodextrin complexes in pharmaceutical and other fields are also explained here with examples. Thus cyclodextrins, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems accompanied with the delivery of different novel drugs through various delivery routes.

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Combined hydroxypropyl-β-cyclodextrin and poly(anhydride) nanoparticles improve the oral permeability of paclitaxel

Cited by 128 publications

References 41 publications

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

Nanoparticules mucopénétrantes : véhicules pour l’administration orale du paclitaxel

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