Study of antifungal activity of amphotericin B-lipid formulations with five lipid carriers

Abstract

Introduction:Invasive pulmonary aspergillosis (IPA) is a prime cause of morbidity and mortality in

immunocompromised individuals, who is undergoing lung transplantation.Mortality among infected

patients is high. Death rate in excess of 90% has been shown in study by Richardson. Most of these

invasive mould infections are acquired through the respiratory tract.An increased incidence of invasive

fungal infection has created major challenges for medical practitioners. Amphotericin B(AmB) has been

the drug of choice for the treatment of many fungal infections, and it is still used as a gold standard

therapy against invasive fungal infection and most commonly used to treat life-threatening conditions

such as cryptococcosis, histoplasmosis, and IPA.Currently, lipid formulations are accepted as a less toxic

alternative to the traditional colloidal dispersion. Drug toxicity, the nephrotoxicity of AmB is the major

clinical problem, which could lead to treatment discontinuation. We designed five lipid formulations of

AmB, and compared the dose-response effects of all lipid formulations in-vitro against three different

fungal strains including Cryptococcus neoformans, Candida albicans and Saccharomyces cerevisiae.

Methods: Five lipid formulations amphotericin B were formulated by lyophilization process. The cylinder plate method performs the relative potency by determining the clear zone of AmB-lipid formulation in the inoculum medium as compared with a clear zone of AmB standard. Broth microdilution method can be used to measure the minimum inhibitory concentration (MIC). The MIC value is based upon predetermined end point, which may be interpreted as an absence of visible growth in a broth containing known concentration of AmB.The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined using Cryptococcus neoformans ATCC 90113 NS and Candida albicans ATCC 90028.

Results: All fiveformulations showed good responses against C. neoformans and Candida albicans, with the MIC and MFC values in the range between 0.16-0.32 µg/ml. The potency of these formulations was equivalent to pure AmB (100%).

Conclusions: The results indicate that the investigateded potassium cholate, potassium deoxycholate, sodium deoxycholate sulfate, sodium cholate and sodium deoxycholate may be used as a promising alternative carrier system for amphotericin B.