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 solu-bility, 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...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/62899 |
| Acceso en línea: | https://hdl.handle.net/10171/62899 |
| Access Level: | acceso abierto |
| Palabra clave: | Área de Biomedicina Camptothecin Nanoparticles Oral delivery Conjugates Cyclodextrin Poly(ethylene glycol) |
| Sumario: | Camptothecin (CPT) exhibits a number of challenges for its oral administration, including a low aqueous solu-bility, 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-beta-CD or methoxy-PEG (m-PEG) to the polymer backbone of GantrezTM 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 nano-particles 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. |
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