Nanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin
Camptothecin (CPT) exhibits a number of challenges for its oral administration, including a low aqueous solubility, a lactone ring susceptible to hydrolysis, and an affinity to the intestinal P-gp. The aim of this work was to evaluate nanoparticles from Gantrez-based conjugates as carriers for the o...
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2021
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oai:doaj.org-article:b0e5b9bcfabe4ba4b626178dcae7dd372021-11-14T04:35:24ZNanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin2590-156710.1016/j.ijpx.2021.100104https://doaj.org/article/b0e5b9bcfabe4ba4b626178dcae7dd372021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2590156721000335https://doaj.org/toc/2590-1567Camptothecin (CPT) exhibits a number of challenges for its oral administration, including a low aqueous solubility, a lactone ring susceptible to hydrolysis, and an affinity to the intestinal P-gp. The aim of this work was to evaluate nanoparticles from Gantrez-based conjugates as carriers for the oral delivery of CPT. For this purpose two different conjugates (G-mPEG and G-HPCD), obtained by the covalent binding of either HP-β-CD or methoxy-PEG (m-PEG) to the polymer backbone of Gantrez™ AN, were synthetized and characterized. Both excipients (m-PEG and HPCD) were selected due to their reported abilities to stabilize the lactone ring of CPT and disturb the effect of intestinal P-gp. The resulting nanoparticles (G-mPEG-NP and G-HPCD-NP) presented a similar size (about 200 nm) and zeta potential (close to −35 mV); although, G-mPEG-NP presented a higher CPT payload than G-HPCD-NP. On the contrary, in rats, nanoparticles based on Gantrez conjugates appeared to be capable of crossing the protective mucus layer and reach the intestinal epithelium, whereas conventional Gantrez nanoparticles displayed a mucoadhesive profile. Finally, the pharmacokinetic study revealed that both formulations were able to enhance the relative oral bioavailability of CPT; although this value was found to be 2.6-times higher for G-mPEG-NP than for G-HPCD-NP.Judit HuarteSocorro EspuelasCristina Martínez-OharrizJuan M. IracheElsevierarticleCamptothecinNanoparticlesOral deliveryConjugatesCyclodextrinPoly(ethylene glycol)Pharmacy and materia medicaRS1-441ENInternational Journal of Pharmaceutics: X, Vol 3, Iss , Pp 100104- (2021) |
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DOAJ |
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EN |
| topic |
Camptothecin Nanoparticles Oral delivery Conjugates Cyclodextrin Poly(ethylene glycol) Pharmacy and materia medica RS1-441 |
| spellingShingle |
Camptothecin Nanoparticles Oral delivery Conjugates Cyclodextrin Poly(ethylene glycol) Pharmacy and materia medica RS1-441 Judit Huarte Socorro Espuelas Cristina Martínez-Oharriz Juan M. Irache Nanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin |
| description |
Camptothecin (CPT) exhibits a number of challenges for its oral administration, including a low aqueous solubility, a lactone ring susceptible to hydrolysis, and an affinity to the intestinal P-gp. The aim of this work was to evaluate nanoparticles from Gantrez-based conjugates as carriers for the oral delivery of CPT. For this purpose two different conjugates (G-mPEG and G-HPCD), obtained by the covalent binding of either HP-β-CD or methoxy-PEG (m-PEG) to the polymer backbone of Gantrez™ AN, were synthetized and characterized. Both excipients (m-PEG and HPCD) were selected due to their reported abilities to stabilize the lactone ring of CPT and disturb the effect of intestinal P-gp. The resulting nanoparticles (G-mPEG-NP and G-HPCD-NP) presented a similar size (about 200 nm) and zeta potential (close to −35 mV); although, G-mPEG-NP presented a higher CPT payload than G-HPCD-NP. On the contrary, in rats, nanoparticles based on Gantrez conjugates appeared to be capable of crossing the protective mucus layer and reach the intestinal epithelium, whereas conventional Gantrez nanoparticles displayed a mucoadhesive profile. Finally, the pharmacokinetic study revealed that both formulations were able to enhance the relative oral bioavailability of CPT; although this value was found to be 2.6-times higher for G-mPEG-NP than for G-HPCD-NP. |
| format |
article |
| author |
Judit Huarte Socorro Espuelas Cristina Martínez-Oharriz Juan M. Irache |
| author_facet |
Judit Huarte Socorro Espuelas Cristina Martínez-Oharriz Juan M. Irache |
| author_sort |
Judit Huarte |
| title |
Nanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin |
| title_short |
Nanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin |
| title_full |
Nanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin |
| title_fullStr |
Nanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin |
| title_full_unstemmed |
Nanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin |
| title_sort |
nanoparticles from gantrez-based conjugates for the oral delivery of camptothecin |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/b0e5b9bcfabe4ba4b626178dcae7dd37 |
| work_keys_str_mv |
AT judithuarte nanoparticlesfromgantrezbasedconjugatesfortheoraldeliveryofcamptothecin AT socorroespuelas nanoparticlesfromgantrezbasedconjugatesfortheoraldeliveryofcamptothecin AT cristinamartinezoharriz nanoparticlesfromgantrezbasedconjugatesfortheoraldeliveryofcamptothecin AT juanmirache nanoparticlesfromgantrezbasedconjugatesfortheoraldeliveryofcamptothecin |
| _version_ |
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