title: pH-driven colloidal transformations based on the vasoactive drug nicergoline.
abstract: The structure of colloidal self-assembled drug delivery systems can be influenced by intermolecular interactions between drug and amphiphilic molecules, and is important to understand in the context of designing improved delivery systems. Controlling these structures can enable controlled or targeted release systems for poorly water-soluble drugs. Here we present the interaction of the hydrophobic vasoactive drug nicergoline with the internal structure of nanostructured emulsion particles based on the monoglyceride-water system. Addition of this drug leads to modification of the internal bicontinuous cubic structure to generate highly pH-responsive systems. The colloidal structures were characterized with small-angle X-ray scattering and visualized using cryogenic transmission electron microscopy. Reversible transformations to inverse micelles at high pH, vesicles at low pH, and the modification of the spacing of the bicontinuous cubic structure at intermediate pH were observed, and enabled the in situ determination of an apparent pKa for the drug in this system--a difficult task using solution-based approaches. The characterization of this phase behavior is also highly interesting for the design of pH-responsive controlled release systems for poorly water-soluble drug molecules.
authors.affiliation: Drug Delivery, Disposition and Dynamics, and §ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus) , 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Salentinig
authors.forename: Kristian J
authors.initials: KJ
authors.lastname: Tangso
authors.forename: Adrian
authors.initials: A
authors.lastname: Hawley
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
mesh_terms: D003102:Colloids / Q000737:chemistry*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009530:Nicergoline / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D003102:Colloids; D014867:Water; D009530:Nicergoline