Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
AG Garro1, DM Beltramo1,2,3, RV Alasino1, V Leonhard1,2, V Heredia1, ID Bianco1,2,41Center of Excellence in Products and Processes of Córdoba; 2National Research Council of Argentina (CONICET); 3School of Chemistry, Catholic University of Córdoba; 4Department of Exact,...
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| Autores principales: | , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2011
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/9fc1913c280045b5a6c5f9ee75b24245 |
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| Sumario: | AG Garro1, DM Beltramo1,2,3, RV Alasino1, V Leonhard1,2, V Heredia1, ID Bianco1,2,41Center of Excellence in Products and Processes of Córdoba; 2National Research Council of Argentina (CONICET); 3School of Chemistry, Catholic University of Córdoba; 4Department of Exact, Physical and Natural Sciences, National University of La Rioja, ArgentinaBackground: We report herein a novel strategy for the preparation of protein-based nanodelivery vehicles for hydrophobic active pharmaceutical ingredients.Methods: The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin.Results: We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin.Conclusion: The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor®-based formulation.Keywords: human serum albumin, paclitaxel, unfolded states, solubility |
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