Stretch-Induced Biodegradation of Polyelectrolyte Multilayer Films for Drug Release Julien Barthes, †,‡,∥ Damien Mertz, †,‡,∥ Charlotte Bach, †,‡ Marie-He ́ le ̀ ne Metz-Boutigue, †,‡ Bernard Senger, †,‡ Jean-Claude Voegel, †,‡ Pierre Schaaf,* ,§ and Philippe Lavalle* ,†,‡ † Institut National de la Santé et de la Recherche Mé dicale, INSERM Unite ́ 977, 11 rue Humann, 67085 Strasbourg Cedex, France ‡ Faculte ́ de Chirurgie Dentaire, Universite ́ de Strasbourg, 1 Place de l’Hô pital, 67000 Strasbourg, France § Centre National de la Recherche Scientifique, UPR22, Institut Charles Sadron, 23 rue du Loess, BP 84047, 67034 Strasbourg, Cedex 2, France * S Supporting Information ABSTRACT: The design of stimuli-responsive polymer assemblies for the controlled release of bioactive molecules has raised considerable interest these two last decades. Herein, we report the design of mechanically responsive drug-releasing films made of polyelectrolyte multilayers. A layer-by-layer (LbL) reservoir containing biodegradable polyelectrolytes is capped with a mechanosensitive LbL barrier and responds to stretching by a total enzymatic degradation of the film. This strategy is successfully applied for the release in solution of an anticancer drug initially loaded within the architecture. ■ INTRODUCTION The design of stimuli-responsive polymer assemblies for the controlled release of bioactive molecules has raised consid- erable interest these two last decades. 1−4 Among the various polymer assemblies, layer-by layer (LbL) polymer films 5 appeared as very promising tools because of their versatile design, 6−8 tunable properties, 9,10 and potential biomedical applications. 11−13 Different stimuli such as light, temperature, pH changes, or chemical reagents were reported to trigger drug and biomacromolecules release initially incorporated within LbL films. 3 To develop new polymer devices suitable for technological applications, the implementation of easier and natural stimuli is however needed. So far, very few studies reported the use of mechanical stretch to release drugs from a polymer matrix despite its simplicity. Our group has recently investigated the use of a mechanical stimulus applied to LbL films to modulate surface hydrophobicity, 14 film permeabil- ity, 15,16 and cellular adhesion 17 or to activate enzymatic catalysis. 18,19 We especially focused our investigations onto LbL films composed of strata playing the role of reservoir of molecules and barrier toward the diffusion of these molecules. Reservoir films are gel-like LbL structures allowing the embedding and free diffusion through the film section of polyelectrolytes, proteins, and drugs. 20 They can act as microcontainers able to deliver molecules to a biological medium. The thickness of these films grows exponentially and reaches several micrometers after a few tens of polyelectrolyte deposition steps. 21 Barrier films are denser, thinner and more structured, reaching only a few tens of nanometers in thickness within a few tens of deposition steps. They can play the role of a tight stratum preventing diffusion of polyelectrolytes and even of small ions. 5 Multicompartment architectures composed of barriers and reservoirs were shown to be ideal systems for the design of stretch-responsive films. For instance, we demon- strated in previous works that such architectures allowed to trigger diffusion of polypeptide chains within reservoir films simply through stretching. 15,16 However, the stretch-induced release of bioactive compounds or drugs from a LbL film to an external medium for delivery application was never reported to our knowledge. ■ RESULTS Herein, we address the design of LbL reservoir films composed of enzymatically degradable biopolymers for the stretch- induced delivery to the solution of loaded drugs (Scheme 1A). Our system is composed of a mechanosensitive barrier made of a poly(allylamine)/poly(styrene sulfonate) (PAH/ PSS) film capped onto a poly(L-lysine)/hyaluronic acid (PLL/ HA) film acting as reservoir. We reported in previous studies 15 the glassy nature of PAH/PSS barriers which form cracks under stretching. This “reservoir/barrier” system is put in contact with a solution of trypsin (TRY), a serine protease enzyme that cleaves C-terminal side of lysine residues from polypeptides, and thus PLL chains. Whereas in the nonstretched state the PAH/PSS barrier is tight and prevents any diffusion of TRY within the film, application of a stretch to the system triggers the diffusion of TRY via openings in the barrier and subsequent Received: June 24, 2012 Revised: September 6, 2012 Published: September 7, 2012 Letter pubs.acs.org/Langmuir © 2012 American Chemical Society 13550 dx.doi.org/10.1021/la302550q | Langmuir 2012, 28, 13550−13554