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Preparation by spray drying of amphotericin B-phospholipid composite particles and their anticellular activity
1Department of Chemical Engineering and Bioprocess Engineering Research Center, Korea Advanced Institute of Science and Technology, Taejon. jinkim@lgcare.co.kr
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 degrees 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.
Insights
Amphotericin B-phospholipid composite particles (APCPs) offer a stable drug delivery system for fungal infections. These particles reduce hemolysis while maintaining antifungal efficacy, overcoming liposomal formulation instability.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Mycology
Background:
- Systemic fungal infections pose a significant therapeutic challenge.
- Amphotericin B (AmB) is a potent antifungal but suffers from toxicity and formulation instability.
- Developing stable and effective AmB delivery systems is crucial.
Purpose of the Study:
- To prepare and characterize amphotericin B-phospholipid composite particles (APCPs) as a drug carrier.
- To evaluate the stability, antifungal activity, and hemolytic properties of APCPs.
- To assess the potential of APCPs in overcoming limitations of conventional AmB formulations.
Main Methods:
- APCPs were prepared using a spray-drying method with AmB and egg phosphatidylcholine.
- Particle morphology was analyzed using scanning and transmission electron microscopy.
- Antifungal activity and hemolytic potential were assessed in vitro.
- Liposome formation and complexation were confirmed via circular dichroism spectroscopy.
Main Results:
- Spherical, submicron-sized APCPs were successfully prepared.
- Hydration of APCPs resulted in liposome-like vesicles and AmB-phospholipid complexes.
- APCPs exhibited reduced hemolytic activity compared to free AmB.
- Antifungal efficacy was preserved, and formulation stability was enhanced.
Conclusions:
- APCPs represent a promising, stable drug delivery system for amphotericin B.
- The composite structure mitigates AmB's inherent toxicity while retaining its antifungal potency.
- Spray-dried APCPs offer an advantage over traditional liposomal formulations due to improved stability.