Abstract
As a potent drug carrier for systemic fungal infections, amphotericin B(AmB)-phospholipid composite particles (APCPs) were prepared by the spray drying method. AmB and egg phosphatidylcholine, co-dissolved in methanol (0.0425-0.45 mg AmB/ml, 0.17-1.8 mg lipid/ml), was nebulized at 2 ml/min. The aerosol produced was carried by air at 1000 ml/min to the inner tubes of a serially connected distilling column system, of which the outer tubes were supplied with circulating water of 95°C. The particles, by scanning electron microphotography,are spherical and submicronsized. Upon hydration of the particles in phosphate-buffered saline for 30 min at room temperature, liposome-like bilayer vesicles were formed along with AmB-phospholipid complexes, evidenced by the transmission electron microphotographs and the positive peak around 330 nm of the circular dichroism spectrum, respectively. The hemolytic abilities of the APCPs were lower than those of free drug, without loss of the antifungal activity. The suppressed hemolysis could be ascribed to the liposomes and to the complexes that are reconstituted by hydration of APCPs. The dry composite particles could circumvent the inherent instability of liposomal formulations.
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