Cluster secondary ion mass spectrometry of polymers and related materials.

Cluster secondary ion mass spectrometry (cluster SIMS) has played a critical role in the characterization of polymeric materials over the last decade, allowing for the ability to obtain spatially resolved surface and in-depth molecular information from many polymer systems. With the advent of new molecular sources such as C(60)(+), Au(3)(+), SF(5)(+), and Bi(3)(+), there are considerable increases in secondary ion signal as compared to more conventional atomic beams (Ar(+), Cs(+), or Ga(+)). In addition, compositional depth profiling in organic and polymeric systems is now feasible, without the rapid signal decay that is typically observed under atomic bombardment. The premise behind the success of cluster SIMS is that compared to atomic beams, polyatomic beams tend to cause surface-localized damage with rapid sputter removal rates, resulting in a system at equilibrium, where the damage created is rapidly removed before it can accumulate. Though this may be partly true, there are actually much more complex chemistries occurring under polyatomic bombardment of organic and polymeric materials, which need to be considered and discussed to better understand and define the important parameters for successful depth profiling. The following presents a review of the current literature on polymer analysis using cluster beams. This review will focus on the surface and in-depth characterization of polymer samples with cluster sources, but will also discuss the characterization of other relevant organic materials, and basic polymer radiation chemistry.

Three-dimensional time-of-flight secondary ion mass spectrometry imaging of a pharmaceutical in a coronary stent coating as a function of elution time.

Three-dimensional (3D) chemical images reveal the surface and subsurface distribution of pharmaceutical molecules in a coronary stent coating and are used to visualize the drug distribution as a function of elution time. The coronary stent coating consists of 25% (w/w) sirolimus in a poly(lactic-co-glycolic acid) (PLGA) matrix and is spray-coated onto metal coupons. Information regarding the 3D distribution of sirolimus in PLGA as a function of elution time was obtained by time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging using a Au(+) ion beam for analysis in conjunction with a C(60)(+) ion beam for sputter depth profiling. The examined formulation is shown to have large areas of the surface as well as subsurface channels that are composed primarily of the drug, followed by a drug-depleted region, and finally, a relatively homogeneous dispersion of the drug in the polymer matrix. Elution is shown to occur from the drug-enriched surface region on a relatively short time scale and more gradually from the subsurface regions of homogeneously dispersed drug. Bulk composition was also probed by X-ray photoelectron spectroscopy (XPS) depth profiling and confocal Raman imaging, the results of which substantiate the TOF-SIMS 3D images. Finally, the effectiveness of a C(60)(+) ion beam for use in 3D characterization of organic systems is demonstrated against another polyatomic ion source (e.g., SF(5)(+)).

Cellular response to phase-separated blends of tyrosine-derived polycarbonates.

Two-dimensional thin films consisting of homopolymer and discrete compositional blends of tyrosine-derived polycarbonates were prepared and characterized in an effort to elucidate the nature of different cell responses that were measured in vitro. The structurally similar blends were found to phase separate after annealing with domain sizes dependent on the overall composition. The thin polymer films were characterized with the use of atomic force microscopy (AFM), water contact angles, and time-of-flight secondary ion mass spectrometry (TOF-SIMS) and significant changes in roughness were measured following the annealing process. Genetic expression profiles of interleukin-1beta and fibronectin in MC3T3-E1 osteoblasts and RAW 264.7 murine macrophages were measured at several time points, demonstrating the time and composition-dependent nature of the cell responses. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) depicted upregulation of the fibronectin gene copy numbers in each of the blends relative to the homopolymers. Moreover, the interleukin-1beta expression profile was found to be compositionally dependent. The data suggest strongly that optimal composition and processing conditions can significantly affect the acute inflammatory and extracellular matrix production responses.

Microstructure and elution of tetracycline from block copolymer coatings.

A critical metrology issue for pharmaceutical industries is the application of analytical techniques for the characterization of drug delivery systems to address interrelationships between processing, structure, and drug release. In this study, cast coatings were formed from solutions of poly(styrene-b-isobutylene-b-styrene) (SIBS) and tetracycline in tetrahydrofuran (THF). These coatings were characterized by several imaging modalities, including time-of-flight secondary ion mass spectrometry (TOF-SIMS) for chemical imaging and analysis, atomic force microscopy (AFM) for determination of surface structure and morphology, and laser scanning confocal microscopy (LSCM), which was used to characterize the three-dimensional structure beneath the surface. The results showed phase separation between the drug and copolymer regions. The size of the tetracycline phase in the polymer matrix ranged from hundreds of nanometers to tens of microns, depending on coating composition. The mass of drug released was not found to be proportional to drug loading, because the size and spatial distribution of the drug phase varied with drug loading and solvent evaporation rate, which in turn affected the amount of drug released.

Phase separation at the surface of poly(ethylene oxide)-containing biodegradable poly(L-lactic acid) blends.

The surface chemistry and in-depth distribution of the composition of a poly(ethylene oxide) (PEO)-containing biodegradable poly(L-lactic acid) (PLLA) blend matrix system have been investigated using X-ray photoelectron spectroscopy (XPS). This study reports detailed quantitative compositional information using a novel numerical method for determining depth profiles. The PEO system studied is an amphiphilic Pluronic P104 surfactant, PEO-b-poly(propylene oxide) (PPO)-b-PEO. The extent of phase separation is analyzed by determining the surface enrichment of the PEO component via measurement of chemical composition at the polymer-air interface. For this blend system, the combination of the PPO component in the Pluronic surfactants drives the formation of a surface excess of Pluronic in the blends with PLLA. The surface excess profile shows a rapid increase in Pluronic surface composition versus bulk Pluronic mass fractions of 1-5%, but the profile levels off above bulk Pluronic mass fractions of 5%.

Three-dimensional compositional analysis of drug eluting stent coatings using cluster secondary ion mass spectrometry.

Cluster secondary ion mass spectrometry (cluster SIMS) employing an SF5+ polyatomic primary ion sputter source in conjunction with a Bi3+ analysis source was used to obtain three-dimensional molecular information in polymeric-based drug-eluting stent coatings. The formulations of the coatings varied from 0% to 50% (w/w) sirolimus drug in poly(lactic-co-glycolic acid) and were prepared on both MP35N metal alloy coupons and bare metal stents. All cluster SIMS depth profiles obtained indicated a drug-enriched surface region, followed by a drug-depletion region, and finally a constant bulk composition region, similar to previous data obtained in polymeric blend systems. The drug overlayer thickness was determined to increase with increasing sirolimus content. Sample temperature was determined to play an important role in the resulting depth profiles, where it was shown that the best profiles were obtained at low temperatures (-100 degrees C). At these temperatures, molecular signals typically remained constant through the entire depth of the film (approximately 6.5 microm) in some cases, as opposed to the typical 1 microm-2 microm depth limit, which is achievable at room temperature. The 3-D imaging capabilities of cluster SIMS were successfully demonstrated and indicated a significant amount of subsurface domain formation in the 25% and 50% sirolimus samples, but not in the 5% sample, which was homogeneous. These results clearly illustrate the utility of cluster SIMS for probing the 3-D structure in polymeric-based drug delivery devices.

Depth profiling of poly(L-lactic acid)/triblock copolymer blends with time-of-flight secondary ion mass spectrometry.

Time-of-flight secondary ion mass spectrometry employing an SF5+ polyatomic primary ion source was utilized to obtain a series of in-depth profiles from PLLA/Pluronic-P104 (poly(ethylene oxide-co-propylene oxide) triblock copolymer) blends in attempts to quantify the in-depth surface segregated Pluronic region. The resultant in-depth profiles were consistent with theoretical models describing the surface segregated region in polymeric blends and copolymer systems, with a surface enriched Pluronic-P104 region, followed by a P104 depletion layer, and finally a constant composition bulk region. These results were consistent over a range of concentrations (1-25%). The depth profiles obtained using cluster SIMS were compared to information obtained using X-ray photoelectron spectroscopy. The results demonstrate that, with cluster primary ion bombardment, we are for the first time able to quantify the polymeric composition as a function of depth within certain multicomponent polymer blends. This success can be attributed to the sputter characteristics of polyatomic primary ion bombardment (SF5+) as compared to monatomic primary ion beams.

Depth profiling of 4-acetamindophenol-doped poly(lactic acid) films using cluster secondary ion mass spectrometry.

The feasibility of using cluster secondary ion mass spectrometry for depth profiling of drug delivery systems is explored. The behavior of various biodegradable polymer films under dynamic SF(5)(+) primary ion bombardment was investigated, including several films doped with model drugs. The SF(5)(+) depth profiles obtained from these biodegradable polymer films showed very little degradation in secondary ion signal as a function of increasing primary ion dose, and it was discovered that the characteristic ion signals for the polymers remained constant for ion doses up to approximately 5 x 10(15) ions/cm(2). These results suggest that the polyester structure of the biodegradable polymers studied here allows for a greater ability to depth profile due to ease of main chain scission. Attempts were also made to depth profile through a series of poly(lactic acid) (PLA) films containing varying concentrations of the drug 4-acetamidophenol. The depth profiles obtained from these films show very little decrease in both the 4-acetamidophenol molecular ion and PLA fragment ion signals as a function of increasing SF(5)(+) primary ion dose. Similar results were obtained with theophylline-doped PLA films. These results show that, in some drug delivery devices, it is possible to monitor the distribution of a drug as a function of depth by using cluster primary ion beams.