Abstract
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-β-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 μg/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 cyclodextrins-poly(anhydride) nanoparticles seems to be an interesting strategy to improve the oral bioavailability of this lipophilic drug.
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Acknowledgements
This work was supported by the Foundation “Caja Navarra: Tú eliges, tú decides” (Nanotechnology and Medicines, number 10828) in Spain. Javier Calvo was also financially supported by GlaxoSmithKline I+D and “Fundación Universidad Empresa” (CITIUS grant) in Spain.
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Calvo, J., Lavandera, J.L., Agüeros, M. et al. Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone. Biomed Microdevices 13, 1015–1025 (2011). https://doi.org/10.1007/s10544-011-9571-1
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DOI: https://doi.org/10.1007/s10544-011-9571-1