Control of drug accessibility on functional polyelectrolyte multilayer films.

A surface coating based on polylysine/hyaluronic acid multilayers was designed and acted as a reservoir for an antiproliferative agent, paclitaxel (Taxol). Absolutely no chemical modification of polyelectrolytes or of the drug was needed and the final architecture was obtained in an extremely simple way using the layer-by-layer method. The paclitaxel dose available for human colonic adenocarcinoma cells HT29 seeded on the films could be finely tuned. Moreover, the accessibility of the drugs was controlled by adding on the top of the drug reservoir a capping made of synthetic polyelectrolyte multilayers. This capping was also required to allow adhesion of HT29 cells. Paclitaxel activity was maintained after embedding in the polyelectrolyte multilayers and cellular viability could be reduced by about 80% 96 h after seeding. The strategy described in this paper could be valuable for various other drug/cell systems.

Polyelectrolyte multilayers and degradable polymer layers as multicompartment films.

Polyelectrolyte multilayers are now a well established concept with numerous potential applications in particular as biomaterial coatings. To timely control the biological activity of cells in contact with a substrate, multicompartment films made of different polyelectrolyte multilayers deposited sequentially on the solid substrate constitute a promising new approach. In a first paper (Langmuir 2004, 20, 7298) we showed that such multicompartment films can be designed by alternating exponentially growing polyelectrolyte multilayers acting as reservoirs and linearly growing ones acting as barriers. In the present study, we first demonstrate however that these barriers composed of synthetic polyelectrolytes are not degraded despite the presence of phagocytic cells. We propose an alternative approach where exponentially growing poly(L-lysine)/hyaluronic acid (PLL/HA) multilayers, used as reservoirs, are alternated with biodegradable polymer layers consisting in poly(lactic-co-glycolic acid) (PLGA) and acting as barriers for PLL chains that diffuse within the PLL/HA reservoirs. We first show that these PLGA layers can be deposited alternatively with PLL/HA multilayers leading to polyelectrolyte multilayer/hydrolyzable polymeric layer films and acting as a reservoirs/barriers system. Bone marrow cells seeded on these films ending by a PLL/HA reservoir rapidly degrade it and internalize the PLL chains confined in this reservoir. Then the cells degraded locally the PLGA barrier and internalize the PLL localized in a lower (PLL/HA) compartment after 5 days of seeding. By changing the thickness of the PLGA layer, we hope to be able to tune the time delay of degradation. Such mixed architectures made of polyelectrolyte multilayers and hydrolyzable polymeric layers could act as coatings allowing us to induce a time scheduled cascade of biological activities. We are currently working on the use of comparable films with compartments filled by proteins or peptides and in which the degradation of the barriers results from a hydrolysis over tunable time scales.

Multicompartment films made of alternate polyelectrolyte multilayers of exponential and linear growth.

The layer by layer deposition process of polyelectrolytes is used to construct films equipped with several compartments containing "free polyelectrolytes". Each compartment corresponds to a stratum of an exponentially growing polyelectrolyte multilayer film, and two consecutive compartments are separated by a stratum composed of a linearly growing multilayer that acts as a barrier preventing polyelectrolyte diffusion from one compartment to another. We use hyaluronic acid/poly(L-lysine) as the system to build the compartments and the poly(styrene sulfonate)/poly(allylamine) system for the barrier. Using confocal microscopy, it is shown that poly(L-lysine) diffuses only within the compartment in which it was initially introduced during the film construction and is thus unable to cross the barriers. Using fluorescein isothiocyanate as a pH indicator, it is also shown that although poly(styrene sulfonate)/poly(allylamine) multilayers act as a barrier for polyelectrolytes, they do not prevent proton diffusion through the film. Such films open the route for multiple functionalization of biomaterial coatings.