Organic-inorganic hybrid polymer coatings with controlled biofunctionality

Fluorinated polyphosphazenes (FPs) offer important advantages as biocompatible coatings for coronary stents and other biomedical devices. Recently, a new class of FPs has been introduced, which integrates carboxylic1,2 or sulfonic acid3 and fluorinated moieties into a single macromolecular structure. Assemblies of such fluorinated polyelectrolytes with polyelectrolytes or charged small functional molecules can offer efficient modulation of hydrophobicity, improved biocompatibility, as well as biofunctionality, such as modulated drug release. Here, we have explored aqueous multilayer polyelectrolyte deposition as a convenient route to nanofabrication of layered coatings built from ionic FPs (iFPs) and polyelectrolytes1,2 or small molecule partners. The resulting layer-by-layer (LbL) assemblies displayed controlled film growth, modulated hydrophobicity, swelling, and protein adsorption characteristics. Hydrophobic interactions largely contributed to the formation of LbL films of iFPs with polycations, leading to linear growth and extremely low water uptake. As shown in neutron reflectometry (NR) studies, films of fluorinated polyphospazenes demonstrated superior layering and persistence of such layering in salt solution as compared to control nonfluorinated polyphospha-zene/polycation films. Hydrophobicity-enhanced ionic pairing between iFP and linear polycations gave rise to large-amplitude oscillations in surface wettability as a function of capping layer. Importantly, hydrophobicity of iFP-capped LbL coatings could be further enhanced by using a highly porous polyester surgical felt rather than planar substrates for film deposition.2 Please click Additional Files below to see the full abstract

Hydrogen-bonded multilayers of a neutral polymer and a polyphenol

We report on association of tannic acid (TA) with neutral or charged polymers in solution and at surfaces and contrast hydrogen-bonded and electrostatically associated polymer/TA complexes and TA/polymer layer-by-layer (LbL) films as per their stability in the pH scale. The neutral polymers used for hydrogen bonding with TA were poly(N-vinylcaprolactam) (PVCL), poly(N-vinylpyrrolidone) (PVPON), poly(ethylene oxide) (PEO), or poly(N-isopropylacrylamide) (PNIPAM), and the polymer used to explore electrostatic binding with TA was 90% quaternized poly (4-vinylpyridine) (Q90). Association of TA with polymers in solution was explored by measuring the turbidity of solutions. At surfaces, LbL film deposition and pH stability were followed by phase-modulated ellipsometry and in-situ Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR). While electrostatically stabilized films of TA with Q90 could not be deposited at low pH values (pH = 2), hydrogen-bonded films of TA with PVCL, PVPON, PEO, and PNIPAM could be constructed at pH 2 and did not dissolve until a critical dissolution pH of 9.5, 9, 8.5, and 8 (measured in 0.01 M buffer solutions) for PVCL/TA, PVPON/TA, PEO/TA, and PNIPAM/TA, respectively. In addition, all multilayers could be also constructed at pH 7.5 in solutions with low ionic strength. The high pH stability of these systems as compared to multilayers of the same neutral polymers with polyacrylic (PAA) or polymethacrylic (PMAA) acids is due to higher pK(a) value of TA of similar to 8.5 as estimated in this paper. We also show that multilayers of TA with a copolymer of N-vinylpyrrolidone containing 20 mol % of primary amino groups, PVPON-NH2-20, were highly stable in a wide pH range from 1.3 to 11.7 because of combined stabilization through both. electrostatic and hydrogen-bonding interactions. For all systems, pH windows for deposition and stability of LbL films at surfaces correlated with the phase behavior of TA complexes in solution. High pH stability of hydrogen-bonded films of TA as well as the capability of tuning the critical pH value for film dissolution in the range close to physiological pH values makes such multilayer systems promising candidates for biomedical applications

Hydrogen-Bonded Hybrid Multilayers: Film Architecture Controls Release of Macromolecules

We report on the construction of purely hydrogen-bonded hybrid polymer multilayers, which are composed of polymer pairs with low- and high- pH stability, and show that the critical pH value of film deconstruction, fraction of components released, and the rate of film dissolution can be tuned in a wide pH range from 3 to 9.5 by varying film composition and architecture. The film building blocks were poly(N-vinylcaprolactam) (PVCL)/poly(L-aspartic acid) (PLAA) bilayers as pairs of hydrogen-bonded polymers with low pH stability (critical disintegration pH of similar to 3.3), and poly(N-vinylcaprolactam) (PVCL)/tannic acid (TA) bilayers as hydrogen-bonded polymers with a higher critical disintegration pH of similar to 9.5. Hybrid TA/PVCL/PLAA multilayers were prepared at low pH using a layer-by-layer technique. Film deposition and pH-induced deconstruction were followed by in situ Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) and phase-modulated ellipsometry. PVCL/TA and PVCL/PLAA pairs were deposited in either alternating or stacked manner. Films with various layer arrangements had drastically different pH dissolution profiles. In all cases, the presence of PVCL/TA layers shifted pH values for release of PLAA from the film to more basic values. In the films with stacked architecture [(PVCL/PLAA)(6) (PVCL/TA)(n)], the mode of film destruction was dependent on both the amount of consecutively deposited PVCL/PLAA pairs and the number of PVCL/TA layer pairs in the surface stack. For the films composed of six bilayers of PVCL/PLAA in the base stack, the critical pH for film disintegration and PLAA release varied with the thickness of the top (PVCL/TA),, stack in a range from pH 3.5 to 5 with n ranging from 0 to 12. In hybrid alternating films, [(PVCL/TA)(1) (PVCL/PLAA)(1)](n) (1:1), release of PLAA and TA was more interdependent. The proximity of PVCL/TA pairs has further delayed PLAA release up to near-neutral pH. In addition, PLAA chains diffusing through the film triggered disruption of PVCL/TA interactions resulting in release of similar to 15-20% of TA. These results demonstrate the effects of proximity and intermixing of hydrogen-bonded polymer pairs of greatly different pH stability on film decomposition modes. The possibility of releasing active molecules and/or polymers combined with the biocompatibility of film components makes such systems attractive candidates for future biomedical applications

Ionically Paired Layer-by-Layer Hydrogels: Water and Polyelectrolyte Uptake Controlled by Deposition Time

Despite intense recent interest in weakly bound nonlinear (“exponential”) multilayers, the underlying structure-property relationships of these films are still poorly understood. This study explores the effect of time used for deposition of individual layers of nonlinearly growing layer-by-layer (LbL) films composed of poly(methacrylic acid) (PMAA) and quaternized poly-2-(dimethylamino)ethyl methacrylate (QPC) on film internal structure, swelling, and stability in salt solution, as well as the rate of penetration of invading polyelectrolyte chains. Thicknesses of dry and swollen films were measured by spectroscopic ellipsometry, film internal structure—by neutron reflectometry (NR), and degree of PMAA ionization—by Fourier-transform infrared spectroscopy (FTIR). The results suggest that longer deposition times resulted in thicker films with higher degrees of swelling (up to swelling ratio as high as 4 compared to dry film thickness) and stronger film intermixing. The stronger intermixed films were more swollen in water, exhibited lower stability in salt solutions, and supported a faster penetration rate of invading polyelectrolyte chains. These results can be useful in designing polyelectrolyte nanoassemblies for biomedical applications, such as drug delivery coatings for medical implants or tissue engineering matrices

Swelling Transitions in Layer-by-Layer Assemblies of UCST Block Copolymer Micelles

An upper critical solution temperature (UCST) block copolymer, poly­(acrylamide-<i>co</i>-acrylonitrile)-<i>b</i>-polyvinyl­pyrrolidone (P­(AAm-<i>co</i>-AN)-<i>b</i>-PVP), was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization, assembled in solution, and deposited within functional layer-by-layer (LbL) temperature-responsive films. In aqueous solutions, the polymer formed well-defined block copolymer micelles (BCMs) at ambient temperature and exhibited a reversible micelle–unimer transition within an ∼40–50 °C temperature range in a wide range of pH and ionic strengths. Temperature-induced dissociation of BCMs to unimers was completely suppressed, however, when BCMs were assembled with tannic acid (TA) within LbL films. Instead, reversible changes in micellar sizes and film swelling occurred as a result of UCST-driven uptake/release of water within/from the micellar cores. The solution pH modulated strength of hydrogen bonding between TA and PVP in the micellar corona, thus strongly affecting film growth, micelle morphology, and film swelling. Spherical micellar morphology and high film swelling degrees were observed with films at neutral pH values, where hydrogen bonding was counteracted by the negative charge of partially ionized TA. In contrast, strong hydrogen bonding and absence of charge in TA caused crumpling of BCMs and reduced the film swelling degree in acidic solutions. Film swelling was also dependent on number of assembled micellar layers, with thicker films exhibiting larger swelling amplitudes and sharper temperature transitions. The LbL assemblies were stable in phosphate buffer saline up to pH 7.5 at 50 °C and preserved their response after 55 heating/cooling cycles. The robustness of the temperature transitions in these films taken together with their occurrence in an aqueous environment in a wide range of pH and ionic strengths makes these films potentially useful for controlling responses of soft interfaces in biological environments

Amphoteric surface hydrogels derived from hydrogen-bonded multilayers: Reversible loading of dyes and macromolecules

We used hydrogen-bonded multilayers of poly(N-vinylpyrrolidone) (PVPON) and poly(methacrylic acid) (PMAA) as precursors for producing surface-bound hydrogels and studied their pH-dependent swelling and protein uptake behavior using in situ attenuated total reflection Fourier transform infrared spectroscopy and in situ ellipsometry. The hydrogels were produced by selective chemical cross-linking between PMAA units using carbodiimide chemistry and ethylenediamine (EDA) as a cross-linking reagent, followed by complete removal of PVPON from the film obtained by exposing the film to pH 7.5. As shown by in situ ellipsometry, hydrogels exhibit distinctive polyampholytic swelling as a function of pH, with minimum swelling at pH 4.2-5.7, and increased film thickness at both lower and higher pH values. Film swelling at lower pH values occurs as a result of the presence of amino groups within the hydrogels, which originate from the one-end attachment of the EDA cross-linker to PMAA chains. The pH-switching of hydrogel swelling was fast and reversible. The degree of hydrogel swelling could be also controlled by varying the time allowed for cross-linking. The produced hydrogels were able to absorb large amounts of dyes and proteins of opposite charge reversibly, in response to pH variations. Finally, we demonstrate that proteins included within the hydrogel can easily be replaced with linear polycations. These surface hydrogels hold promise for bioseparation and controlled delivery applications