Influence of the vehicle on the properties and efficacy of microparticles containing amphotericin B

Abstract

New microparticles containing amphotericin B (AMB) have been developed and manufactured by spray drying. To this end albumin, polylactic-co-glycolic acids (PLGA) and poly(sebacic anhydride) have been employed as drug carriers. The selection of the solvent used to disperse the drug and the vehicle before spray drying was critical on production yields and physical properties of the microparticles. Once particle size, morphology and dispersability in some aqueous media were shown to be acceptable for an intravenous administration, in vivo efficacy was evaluated and compared with the reference medicine Fungizone®. Microparticles prepared with albumin, albumin heated at a high temperature, some kinds of PLGA or polyanhydride, as well as Fungizone®, were tested in an experimental hamster model of infection with Leishmania infantum, by evaluating the evolution of parasitic burdens in spleen, liver and antibody responses. After the injection of three doses corresponding to 2 mg of AMB per kilogram each, diverse reactions were reported depending on the vehicle. The best dispersability, reduction of parasites and antibody response were achieved when the treatment was performed with AMB in albumin microspheres.

Keywords::

• Dispersability
• amphotericin B
• albumin microspheres
• microparticles