title: Influence of aggregation on interaction of lipophilic, water-insoluble azaphthalocyanines with DOPC vesicles.
abstract: Dioleoylphosphatidylcholine unilamellar vesicles made by extrusion technique (LUVETs) were studied as the delivery system for lipophilic water-insoluble potential photosensitizers for photodynamic therapy (PDT). Two azaphthalocyanines (AzaPcs) with hydrophobic substituents only and two also possessing two charged amino groups were introduced into the study. All compounds are insoluble in water and form aggregates in PBS with tetrahydrofuran as cosolvent. The size of these aggregates depends on the concentration of AzaPc in solution. AzaPcs with tert-butyl substituents were found to be incorporated into the lipid bilayer of vesicles in the monomeric form even at high concentrations. The stability of LUVETs with incorporated AzaPc was excellent for at least 4 weeks. Therefore, they are suitable for use as a delivery system for these water-insoluble photosensitizers. Very low amount of AzaPc with n-octyl substituents incorporated into LUVETs due to its stronger self-aggregation. Values of binding constants determined for all AzaPcs showed inverse order than expected from their lipophilicities. However, the binding constants followed the order of the strength of aggregation forces. Aggregation of AzaPcs in water medium plays a very important role in the interaction of AzaPcs with LUVETs.
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Prague, Czech Republic. pretr.zimcik@faf.cuni.cz
authors.forename: Petr
authors.initials: P
authors.lastname: Zimcik
authors.forename: Miroslav
authors.initials: M
authors.lastname: Miletin
authors.forename: Kamil
authors.initials: K
authors.lastname: Kopecky
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Musil
authors.forename: Pavel
authors.initials: P
authors.lastname: Berka
authors.forename: Veronika
authors.initials: V
authors.lastname: Horakova
authors.forename: Helena
authors.initials: H
authors.lastname: Kucerova
authors.forename: Jarmila
authors.initials: J
authors.lastname: Zbytovska
authors.forename: Daniel
authors.initials: D
authors.lastname: Brault
mesh_terms: D001372:Aza Compounds / Q000737:chemistry*; D003486:Cyanides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D015394:Molecular Structure; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D010795:Phthalic Acids / Q000737:chemistry*; D012995:Solubility; D013053:Spectrophotometry; D014867:Water / Q000737:chemistry*
chemical_list: D001372:Aza Compounds; D003486:Cyanides; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D010795:Phthalic Acids; D014867:Water; C017251:1,2-oleoylphosphatidylcholine