Antifungal nanoparticles for targeted treatment of fungal infections

Abstract

The invention provides functionalized antifungal-loaded liposomal formulations targeting Candida, which minimize damage to healthy human cells, limit antimicrobial exposure, and reduce the development of antifungal resistance.

We claim: 
     
         1 . A composition comprising a liposomal formulation and an antifungal. 
     
     
         2 . The composition of  claim 1 , wherein the liposomal formulation is a unilamellar liposomal formulation. 
     
     
         3 . The composition of  claim 1 , wherein the antifungal is selected from the group consisting of antifungal lipopeptides, azoles, polyenes, allylamines, and nucleosides. 
     
     
         4 . The composition of  claim 1 , wherein the antifungal is an antifungal echinocandin. 
     
     
         5 . The composition of  claim 1 , wherein the antifungal is selected from the group consisting of anidulafungin, echinocandin B, cilofungin, micafungin, and caspofungin. 
     
     
         6 . The composition of  claim 1 , further comprising a P-113Q2.10-PEG lipid decoration or a palmitic acid decoration. 
     
     
         7 . The composition of  claim 1 , further comprising dectin-1. 
     
     
         8 . The composition of  claim 1 , further comprising a P-113Q2.10-PEG lipid decoration and dectin-1. 
     
     
         9 . A method of making a liposomal formulation, comprising the steps of a freeze-thaw, sonication, and extrusion method, wherein the liposomal formulation comprises the lipids hydrogenated soy phosphatidylcholine, cholesterol, phosphatidylglycerol, and α-tocopherol, and an antifungal selected from the group consisting of, but not limited to, anidulafungin, echinocandin B, cilofungin, micafungin, and caspofungin. 
     
     
         10 . The method of  claim 9 , wherein the liposomal formulation comprises the lipids hydrogenated soy phosphatidylcholine, cholesterol, phosphatidylglycerol, and α-tocopherol, and the antifungal at a mass concentration (% w/w) of 60.73%, 14.83%, 23.95%, 0.18%, and 0.31% respectively. 
     
     
         11 . The method of  claim 9 , wherein the liposomal formulation comprises of any lipid or lipid-like structure, natural or synthetic, or any amphiphilic molecule or combination of, and an antifungal, decorated with P-113Q2.10 and dectin-1 targeting moieties. 
     
     
         12 . The method of  claim 9 , wherein the liposomes have an average diameter of 100 to 1000 nm (polydispersity index (PDI)=0 to 0.5). 
     
     
         13 . The method of  claim 9 , further comprising the steps of measuring vesicle size and PDI using dynamic light scattering (DLS). 
     
     
         14 . A method for treating a  Candida  infection, comprising the step of administering a liposomal formulation comprising an antifungal lipopeptide to a subject with a  Candida  infection. 
     
     
         15 . The method of  claim 14 , wherein the  Candida  infection is a bloodstream  Candida  infection, and wherein the administering step comprises administering the liposomal formulation to a subject with a bloodstream  Candida  infection. 
     
     
         16 . The method of  claim 14 , wherein the  Candida  infection is candidiasis, and wherein the administering step comprises administering the liposomal formulation to a subject with candidiasis. 
     
     
         17 . The method of  claim 14 , wherein the  Candida  infection is systemic candidiasis, and wherein the administering step comprises administering the liposomal formulation to a subject with systemic candidiasis. 
     
     
         18 . The method of  claim 14 , wherein the  Candida  infection is a  Candida  biofilm, and wherein the administering step comprises administering the liposomal formulation to a subject with a  Candida  biofilm. 
     
     
         19 . The method of  claim 14 , wherein the liposomal formulation has a minimum inhibitory concentration range of 1.5 to 12.5 μg/mL. 
     
     
         20 . The method of  claim 14 , where the treatment reduces fungal burden by five-fold after only 24 hours.