Self-Assembled Teicoplanin Micelles as Amphotericin B Nanocarrier.

Teicoplanin (Teico) is an antimicrobial agent that spontaneously forms micelles in aqueous media. In this work, we characterized the physicochemical properties of nanoparticles formed by the interaction of Teico with Amphotericin B (AmB). Teico-AmB micelles structure spontaneously in aqueous media, with a particle size of 70-100 nm and a zeta potential of -28 mV. Although the characterization of these nanostructures yielded satisfactory results, in vitro cytotoxicity tests showed high toxicity. Based on this, adding cholesterol to the formulation was evaluated to try to reduce the toxicity of the drug. These Teico-AmB-Chol nanostructures have a larger size, close to 160 nm, but a lower polydispersity index. They also showed strongly negative surface charge and were more stable than Teico-AmB, remaining stable for at least 20 days at 4 °C and 25 °C and against centrifugation, dilution, freezing, lyophilization and re-suspension processes with a recovery percentage of AmB greater than 95%, maintaining their initial size and zeta potential. These Teico-AmB-Chol micelles show lower cytotoxic effect and higher biological activity than Teico-AmB, even than Amfostat® and Ambisome® formulations. These two new nanoparticles, with and without Chol, are discussed as potential formulations able to improve the antifungal therapeutic efficiency of AmB.

Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes.

BACKGROUND: 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.