PMID- 22770505 OWN - NLM STAT- MEDLINE DCOM- 20130306 LR - 20181201 IS - 1543-8392 (Electronic) IS - 1543-8384 (Linking) VI - 9 IP - 9 DP - 2012 Sep 4 TI - Interactions of liposome carriers with infectious fungal hyphae reveals the role of beta-glucans. PG - 2489-96 LID - 10.1021/mp300097k [doi] AB - 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 beta-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 beta-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. FAU - Chavan, Neelam L AU - Chavan NL AD - Department of Pharmacological & Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas 77030, United States. FAU - Young, Joseph K AU - Young JK FAU - Drezek, Rebekah A AU - Drezek RA FAU - Lewis, Russell AU - Lewis R FAU - Bikram, Malavosklish AU - Bikram M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120802 PL - United States TA - Mol Pharm JT - Molecular pharmaceutics JID - 101197791 RN - 0 (Aniline Compounds) RN - 0 (Antifungal Agents) RN - 0 (Drug Carriers) RN - 0 (Echinocandins) RN - 0 (Glucans) RN - 0 (Lipopeptides) RN - 0 (Liposomes) RN - 0 (Polysaccharides) RN - 0 (beta-Glucans) RN - 0 (liposomal amphotericin B) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 7XU7A7DROE (Amphotericin B) RN - 8004-91-9 (aniline blue) RN - 9008-22-4 (laminaran) RN - F0XDI6ZL63 (Caspofungin) SB - IM MH - Amphotericin B/*pharmacokinetics/pharmacology MH - Aniline Compounds/pharmacology MH - Antifungal Agents/pharmacokinetics/pharmacology MH - Aspergillus fumigatus/drug effects/*metabolism MH - Candida albicans/drug effects/*metabolism MH - Caspofungin MH - Cell Wall/drug effects/metabolism MH - Chemistry, Pharmaceutical/methods MH - Drug Carriers/*pharmacokinetics MH - Echinocandins/pharmacology MH - Glucans MH - Hyphae/drug effects/*metabolism MH - Lipopeptides MH - Liposomes/*pharmacokinetics MH - Models, Molecular MH - Polyethylene Glycols/chemistry MH - Polysaccharides/pharmacology MH - beta-Glucans/*metabolism EDAT- 2012/07/10 06:00 MHDA- 2013/03/07 06:00 CRDT- 2012/07/10 06:00 PHST- 2012/07/10 06:00 [entrez] PHST- 2012/07/10 06:00 [pubmed] PHST- 2013/03/07 06:00 [medline] AID - 10.1021/mp300097k [doi] PST - ppublish SO - Mol Pharm. 2012 Sep 4;9(9):2489-96. doi: 10.1021/mp300097k. Epub 2012 Aug 2.