Composite multilayered biocompatible polyelectrolyte films with intact liposomes: stability and temperature triggered dye release

Abstract

The design of new quasi-2D biocompatible films able to release a drug in a controlled manner through the application of physical stimuli is of outstanding interest in biomaterials science. Herein, construction of composite nanofilms with multiple strata of stabilized large unilamellar liposomes is developed. The film has a multilayered architecture formed by the layer-by-layer (LbL) technique utilising two biocompatible polyelectrolytes, hyaluronic acid and poly-L-lysine (HA and PLL), onto which phospholipid liposome “interlayers” are adsorbed and subsequently embedded by further polyelectrolyte adsorption. First of all the morphology of the film surface is characterised and compared to the morphology obtained for a film containing the same polyelectrolytes but stiff polystyrene (PS) latex particles instead of the soft phospholipid vesicles. Both morphologies appear to be similar suggesting that the embedded vesicles keep their spherical shape. As a second step, it has been shown that carboxyfluorescein (CF) encapsulated in the vesicles remains inside without sustained release at room temperature indicating that the liposomes stay intact upon LbL immobilization. A substantial fraction (about 70%) of the vesicles absorbed onto the polyelectrolyte film are desorbed upon further polyelectrolyte adsorption to reach the embedded state. Hence to achieve high loading of the film, multiple vesicle depositions have to be performed. It is shown that the total number of deposited vesicles on the film is proportional to the number m of vesicle deposition steps (up to m = 3). The encapsulated dye can be released in a controlled manner by a temperature increase above the main phase transition temperature of the lipid mixture used to prepare the vesicles. Release kinetics is faster for film-entrapped vesicles than for those in solution due to destabilization of the lipidic bilayer by the polyelectrolyte environment. The developed composite films represent a new surface biocoating able to preserve, in native state, or to release in a controlled way, surface immobilized materials under external stimuli.