Multifunctional carriers for controlled drug delivery

Abstract

Abstract In the review we describe a method for concentration of anionic liposomes with encapsulated water-soluble substances within a small volume via electrostatic liposome adsorption on the surface of polymer particles with grafted cationic chains (spherical polycationic brushes), or cationic microgel particles. Dozens of intact liposomes can be bound to each polymer particle, the resulting polymer/liposome complex does not dissociate into the original components in a physiological solution. This allows fabrication of multi-liposomal complexes (MLCs) with a required ratio of encapsulated substances. Two approaches are discussed for the synthesis of stimuli-sensitive MLCs. The first is to incorporate the conformation switch, morpholinocyclohexanol-based lipid, into the liposomal membrane thus forming pH-sensitive liposomes capable of releasing their cargo when acidifying the surrounding solution. These liposomes complexed with the brushes release encapsulated substances much faster than the uncomplexed liposomes. The second is to adsorb liposomes on cationic thermo-responsive microgels. The resulting MLCs contracts upon heating over a volume phase transition temperature from the swollen to the collapsed state of microgel, thus causing the adsorbed liposomes to change drastically their morphology and release an encapsulated substance. Complexation of anionic liposomes with chitosan microgels and polylactide micelles gives MLCs which degrade in the presence of enzymes down to small particles, 10–15 nm in diameter. A novel promising approach suggests that immobilized liposomes can act as a capacious depot for biologically active compounds and ensure their controllable leakage to surrounding solution.