title: Interactions of liposome carriers with infectious fungal hyphae reveals the role of β-glucans.
abstract: Relatively little is known about how liposomal formulations modulate drug delivery to fungal pathogens. We compared patterns of hyphal cell wall binding for empty rhodmine-labeled liposomes and the clinically available amphotericin B-containing liposomal formulation (AmBisome) in  Aspergillus fumigatus  and  Candida albicans.  Following 0.5 h of coincubation with  A. fumigatus , empty liposomes concentrated primarily in fungal septae along at the surface of the cell wall, suggesting that liposome uptake is concentrated in areas of the cell wall where linear glucan is exposed on the cell surface, which was confirmed by aniline blue staining. Consistent with this hypothesis, pretreatment of liposomes with soluble linear glucan (laminarin) decreased liposome binding in both  Aspergillus  and  Candida  fungal hyphae, while growth of  Aspergillus  hyphae in the presence of an agent that increases fungal cell wall surface exposure of linear β-glucans without cell death (caspofungin) increased liposome uptake throughout the  Aspergillus  fungal cell wall. Increasing the polyethylene glycol (PEG) concentration in liposomes from 0 to 30% significantly increased fungal uptake of liposomes that was only modestly attenuated when fungal cells were incubated in serum concentrations ranging from 10 to 100%. The presence of β-glucans on the fungal hyphae cell walls of  Aspergillus fumigatus  is one of the factors responsible for mediating the binding of liposome carriers to the hyphae and could explain possible synergy reported between liposomal amphotericin B and echinocanins.
authors: Department of Pharmacological & Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas 77030, United States.
authors: Neelam L
authors: NL
authors: Chavan
authors: Joseph K
authors: JK
authors: Young
authors: Rebekah A
authors: RA
authors: Drezek
authors: Russell
authors: R
authors: Lewis
authors: Malavosklish
authors: M
authors: Bikram
mesh_terms: D000666:Amphotericin B / Q000493:pharmacokinetics* / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism*; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000493:pharmacokinetics*; D054714:Echinocandins / Q000494:pharmacology; D005936:Glucans; D025301:Hyphae / Q000187:drug effects / Q000378:metabolism*; D055666:Lipopeptides; D008081:Liposomes / Q000493:pharmacokinetics*; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry; D011134:Polysaccharides / Q000494:pharmacology; D047071:beta-Glucans / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D000935:Antifungal Agents; D004337:Drug Carriers; D054714:Echinocandins; D005936:Glucans; D055666:Lipopeptides; D008081:Liposomes; D011134:Polysaccharides; D047071:beta-Glucans; C068538:liposomal amphotericin B; D011092:Polyethylene Glycols; D000666:Amphotericin B; C017006:aniline blue; C008247:laminaran; D000077336:Caspofungin