Interaction of amphotericin B with polymeric colloids: 2. Effect of poloxamer on the adsorption of amphotericin B onto poly(ϵ-caprolactone) nanospheres

Electronic absorption and circular dichroism measurements of poloxamer 188-free amphotericin B-nanospheres, as compared with those previously recorded from AmB–poloxamer and free amphotericin B (AmB), revealed that AmB self-aggregation was drastically reduced when AmB is associated with poly(ϵ-caprolactone) alone. The present work showed the ability of poloxamer to disturb this organization of AmB due to competition between the drug and poloxamer for adsorption at the surface of nanospheres. The increasing amounts of free AmB measured in the supernatant and the decrease of zeta potential of AmB-nanospheres (which was related to AmB adsorbed onto the spheres) with increasing poloxamer concentration confirmed the inhibition of the adsorption of AmB by these surfactants. Moreover, considering that most part of the surfactant was in excess and remained in the supernatant, this could have led to the formation of AmB–poloxamer mixed micelles, as suggested by the similarity between AmB–poloxamer spectra and those of AmB-nanospheres with high amounts of poloxamer. Further evidence of this competitive adsorption was obtained when AmB-nanospheres were prepared with poloxamer of various nature: differing in the length of the poly(propylene oxide) region and the molecular weight. Reduction of adsorption of the drug onto the surface seems to be particularly favoured by the presence of a surfactant such as poloxamer 407 which possesses a large propylene oxide (PPO) unit.