Infant dietary exposure to dioxin-like polychlorinated biphenyls (dlPCBs), polybrominated and mixed halogenated dibenzo-p-dioxins and furans (PBDD/Fs and PXDD/Fs) in milk samples of lactating mothers in Accra, Ghana.

In this study, polybrominated and mixed halogenated dibenzo-p-dioxins and furans (PBDD/Fs and PXDD/Fs), and dioxin-like polychlorinated biphenyls (dlPCBs) were quantified in 24 human milk samples of first-time lactating mothers from Greater Accra region in Ghana. The aims of the study were to determine the concentrations and toxic equivalent concentrations of PBDD/F, PXDD/F and dlPCBs in human milk, and to estimate an infant's daily intake. The samples were analysed for 12 dioxin-like PCBs, 7 congeners of 2,3,7,8-polybrominated dibenzo-p-dioxins and furans (PBDD/Fs), and 7 congeners of 2,3,7,8-mixed halogenated dioxins and furans (PXDD/Fs, where X = Br/Cl). The mean concentrations in human milk ranged from 0.15 to 212.9 pg/g lipid for dlPCB congeners (mean TEQ: 1.67 pg WHO2005-TEQ/g lipid). Lesser concentrations for 2,3,7,8-PXDD/Fs (and PBDD/Fs congeners) ranged between <0.01-1.67 pg/g lipid, with a total mean tentative TEQ of 0.56 pg WHO2005-TEQ/g lipid. For an infant of average weight 7 kg, consuming an estimated volume of 600 mL human milk, the estimated average daily intake of dlPCBs in 21 human milk samples was 4.95 pg TEQ/kg bw/day; contributions from dlPCBs, PXDD/Fs and PBDD/Fs resulted in an average estimated daily intake of 6.56 pg TEQ/kg bw/day. The results obtained in this study, although lower than infant dietary intake estimates in human milk from industrialized countries, exceeded the recommended safety standards of 1 pg TEQ/kg bw/day and 1-4 pg TEQ/kg bw/day from the Agency for Toxic Substances and Disease Registry (ATSDR) and the World Health Organization (WHO), respectively.

ToF-SIMS and TIRF microscopy investigation on the effects of HEMA copolymer surface chemistry on spatial localization, surface intensity, and release of fluorescently labeled keratinocyte growth factor.

The need for direct biomaterial-based delivery of growth factors to wound surfaces to aid in wound healing emphasizes the importance of interfacial interactions between the biomaterial and the wound surface. These interactions include the spatial localization of growth factor, the surface intensity of growth factor in contact with the wound, and the release profile of growth factor to the wound surface. The authors report the use of time-of-flight secondary ion mass spectrometry to determine the relationship between biomaterial surface chemistry and the spatial localization of growth factor. They have implemented a novel application of total internal reflectance fluorescence (TIRF) microscopy to measure the surface intensity and release of growth factor in contact with a glass substrate that has been used to model a wound surface. Detailed information regarding TIRF experiments has been included to aid in future studies regarding the biomaterial delivery to interfaces. The authors have evaluated the effects of (hydroxyethyl)methacrylate (HEMA) homopolymer, 5.89% methyl methacrylate/HEMA, and 5.89% methacrylic acid/HEMA surface chemistry on the spatial localization of AlexaFluor 488-labeled keratinocyte growth factor (AF488-KGF), AF488-KGF surface intensity at the copolymer surface, and release to a glass substrate. KGF is known to promote re-epithelialization in wound healing. The results show that the two copolymers allow for increased surface coverage, surface intensity, and release of AF488-KGF in comparison to the homopolymer. It is likely that differences in these three aspects could have a profound effect on the wound healing response.

The state of POPs in Ghana- A review on persistent organic pollutants: Environmental and human exposure.

Ghana is one of the top pesticide users and highest persistent organic pollutant (POP) emitters in sub-saharan Africa. Despite recent increases in published data, there is limited information on how POP concentrations have changed, post ratification of the Stockholm Convention. As a result, this review aims to address these knowledge gaps by collating available data that reported POPs in Ghanaian environmental matrices, identify spatial and temporal trends, and establish potential health risks. It is worth noting that Ghana has not developed its own regulatory standards for POPs, but adapts United States Environmental Protection Agency (USEPA) standards. Results obtained showed concentrations in excess of USEPA regulatory standards for per- and poly-fluoroalkyl sulphonates (PFASs) and dichlorodiphenyldichloroethane (DDD) in water, polychlorinated and polybrominated dibenzo-p-dioxins and furans (PCDD/Fs and PBDD/Fs) in e-waste soils, and polybrominated diphenyl ethers in aquatic organisms and dairy products. The published studies do not cover major regions nationwide. The inconsistency in methods and analytes measured, along with data scarcity in some regions, makes it challenging to identify temporal trends. However, the data did indicate decreasing concentrations of some legacy POPs in soil/sediment and aquatic organisms, with increasing concentrations of some POPs in water, fish, fruits and vegetables. Studies that performed health risks assessments were limited although the data indicated risks to e-waste workers, some farmers and vulnerable sub-populations. This review identified potential human health risks from POPs in the Ghanaian environment and the need for more consistent and widespread monitoring program.

Background levels of dioxin-like polychlorinated biphenyls (dlPCBs), polychlorinated, polybrominated and mixed halogenated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, PBDD/Fs & PXDD/Fs) in sera of pregnant women in Accra, Ghana.

Human exposure data on dioxins and dioxin-like compounds (DLCs) in Ghana are limited. Based on health risks associated with dioxins and DLCs, the impact of maternal body burdens on foetal exposure is significant. This is the first study that assesses polychlorinated, polybrominated and mixed halogenated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, PBDD/Fs and PXDD/Fs), and dioxin-like polychlorinated biphenyls (dlPCBs) in sera of primiparous Ghanaians. Our sample selection includes 34 participants from two municipalities (Accra and Tema), and explores contributions from environmental and dietary exposures using questionnaire data. Sample preparation involved C18 solid phase extraction, purification with acidified silica and lipid removal cartridges, and detection with gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. The calculated average toxic equivalent concentration was 5.3 pg TEQ/g lw, with contributions from dlPCBs (1.25 pg TEQ/g lw), PCDD/Fs (3.10 pg TEQ/g lw), PBDD/Fs (0.49 pg TEQ/g lw) and PXDD/Fs (0.50 pg TEQ/g lw). The calculated total TEQ concentration was lower than background TEQ concentrations reported in sera of pregnant women globally. Positive correlations were obtained for total dioxins and DLC concentrations with age and Body Mass Index (BMI). Dietary intake of seafood and dairy products had a strong influence on PCDD/F and dlPCB concentrations. Statistically significant differences were observed for dioxins and DLCs in participants from Accra (in close proximity to Agbogbloshie e-waste site) and Tema. Given the significant TEQ contribution of PBDD/Fs and PXDD/Fs (~20%), it is essential to explore these classes of dioxins and DLCs in future biomonitoring studies as they may pose health risks, and add extra diagnostic information in source exposure investigations.

Spatial analysis of time of flight-secondary ion mass spectrometric images by ordinary kriging and inverse distance weighted interpolation techniques.

Ordinary kriging and inverse distance weighted (IDW) are two interpolation methods for spatial analysis of data and are commonly used to analyze macroscopic spatial data in the fields of remote sensing, geography, and geology. In this study, these two interpolation techniques were compared and used to analyze microscopic chemical images created from time of flight-secondary ion mass spectrometry images from a patterned polymer sample of fluorocarbon (C(x)F(y)) and poly(aminopropyl siloxane) (APS, a.k.a. siloxane). Data was eliminated from the original high-resolution data set by successive random removal, and the image file was interpolated and reconstructed with a random subset of points using both methods. The statistical validity of the reconstructed image was determined by both standard geographic information system (GIS) validation statistics and evaluating the resolution across an image boundary using ASTM depth and image resolution methodology. The results show that both ordinary kriging and IDW techniques can be used to accurately reconstruct an image using substantially fewer sample points than the original data set. Ordinary kriging performed better than the IDW technique, resulting in fewer errors in predicted intensities and greater retention of original image features. The size of the data set required for the most accurate reconstruction of the original image is directly related to the autocorrelation present within the data set. When 10% of the original siloxane data set was used for an ordinary kriging interpolation, the resulting image still retained the characteristic gridlike pattern. The C(x)F(y) data set exhibited stronger spatial correlation, resulting in reconstruction of the image with only 1% of the original data set. The removal of data points does result in a loss of image resolution; however, the resolution loss is not directly related to the percentage of sample points removed.

Formation of high-mass cluster ions from compound semiconductors using time-of-flight secondary ion mass spectrometry with cluster primary ions.

The detection of high-mass, nonstoichiometric, GaxAsy and InxPy secondary ion clusters using time-of-flight secondary ion mass spectrometry is reported for the first time. The GaxAsy and InxPy clusters are detected in both positive and negative ion spectra and extend to masses of at least 6000 dalton (Da). Consecutive clusters differ by the addition of one gallium (indium) atom. This leads to nonstoichiometric clusters at high mass (i.e., Ga15As3 at 1270 Da) which are metastable above a critical mass. The relative secondary ion yields of high-mass GaxAsy clusters detected using several primary ion sources (Cs+, Bi+, Bi3+, Bi32+, Bi52+, C60+, and C602+) are compared. The relative secondary ion yield of high-mass GaxAsy clusters is significantly enhanced by the use of cluster primary ions and the best relative secondary ion yield is obtained using Bi3+ primary ions. An application of the high-mass GaxAsy clusters is presented, in which these clusters are utilized to distinguish between contaminant levels of Ga and bulk GaAs structure in a depth profile of a MnAs/GaAs heterojunction. These results illustrate improved analysis of inorganic materials using cluster primary ions and break the paradigm of stoichiometric secondary cluster ion formation for SIMS of inorganic compounds.

Guest aggregation within poly(L-lactic acid)/pluronic P104 thin films.

Rhodamine 6G (R6G) doped thin films composed of poly(L-lactic acid) (PLLA) and Pluronic P104 were spin cast onto glass microscope slides and characterized by ultraviolet-visible, steady-state, and time-resolved fluorescence spectroscopy. The results show that R6G aggregation within the film increases as the R6G concentration and P104 loading increases. These results suggest an approach for studying drug distributions (monomers, aggregates) within biodegradable polymer formulations.

Quantitative ToF-SIMS Studies of Protein Drug Release from Biodegradable Polymer Drug Delivery Membranes.

Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system.Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/z 467 and 421, respectively. These peaks were determined to be [AOT + Na+] and [AOT-Na+]-. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution.

Differential orientation and conformation of surface-bound keratinocyte growth factor on (hydroxyethyl)methacrylate, (hydroxyethyl)methacrylate/methyl methacrylate, and (hydroxyethyl)methacrylate/methacrylic acid hydrogel copolymers.

The development of hydrogels for protein delivery requires protein-hydrogel interactions that cause minimal disruption of the protein's biological activity. Biological activity can be influenced by factors such as orientational accessibility for receptor binding and conformational changes, and these factors can be influenced by the hydrogel surface chemistry. (Hydroxyethyl)methacrylate (HEMA) hydrogels are of interest as drug delivery vehicles for keratinocyte growth factor (KGF) which is known to promote re-epithelialization in wound healing. The authors report here the surface characterization of three different HEMA hydrogel copolymers and their effects on the orientation and conformation of surface-bound KGF. In this work, they characterize two copolymers in addition to HEMA alone and report how protein orientation and conformation is affected. The first copolymer incorporates methyl methacrylate (MMA), which is known to promote the adsorption of protein to its surface due to its hydrophobicity. The second copolymer incorporates methacrylic acid (MAA), which is known to promote the diffusion of protein into its surface due to its hydrophilicity. They find that KGF at the surface of the HEMA/MMA copolymer appears to be more orientationally accessible and conformationally active than KGF at the surface of the HEMA/MAA copolymer. They also report that KGF at the surface of the HEMA/MAA copolymer becomes conformationally unfolded, likely due to hydrogen bonding. KGF at the surface of these copolymers can be differentiated by Fourier-transform infrared-attenuated total reflectance spectroscopy and time-of-flight secondary ion mass spectrometry in conjunction with principal component analysis. The differences in KGF orientation and conformation between these copolymers may result in different biological responses in future cell-based experiments.

Uptake and transformations of engineered nanomaterials: Critical responses observed in terrestrial plants and the model plant Arabidopsis thaliana.

With the applications of engineered nanomaterials (ENMs) continually expanding and production quickly growing, residues of ENMs will end up in the environment at levels that may be harmful to non-target organisms. Many of the tunable properties that have made them desirable, such as type, size, charge, or coating, also contribute to the current difficulties in understanding the fate of ENMs in the environment. This review article focuses on studies that investigate plant-ENM interactions, including techniques used to study these interactions and documented plant responses due to the phytotoxic effects of ENMs. The many variables which can be altered for an experiment, such as type, size, and concentration of ENMs, make it difficult to formulate generalizations about the uptake mechanism involved, or to make an inference on the subcellular localization and distribution of the internalized ENMs in plant tissue. In order to avoid these challenges, studies can utilize a model organism such as Arabidopsis thaliana, and a combination of analytical techniques that can reveal complementary information in order to assess how the different experimental conditions influence the uptake and phytotoxicity of ENMs. This review presents recent studies regarding plant-ENM interactions employing Arabidopsis to demonstrate how the use of this model plant can advance our understanding of plant-ENM interactions and guide additional studies using other plant species. Overarching results suggest that more sensitive tests and consistency in experimental designs are needed to fully assess and understand the phytotoxic effects of ENMs in the environment.

Segment fusion of ToF-SIMS images.

The imaging capabilities of time-of-flight secondary ion mass spectrometry (ToF-SIMS) have not been used to their full potential in the analysis of polymer and biological samples. Imaging has been limited by the size of the dataset and the chemical complexity of the sample being imaged. Pixel and segment based image fusion algorithms commonly used in remote sensing, ecology, geography, and geology provide a way to improve spatial resolution and classification of biological images. In this study, a sample of Arabidopsis thaliana was treated with silver nanoparticles and imaged with ToF-SIMS. These images provide insight into the uptake mechanism for the silver nanoparticles into the plant tissue, giving new understanding to the mechanism of uptake of heavy metals in the environment. The Munechika algorithm was programmed in-house and applied to achieve pixel based fusion, which improved the spatial resolution of the image obtained. Multispectral and quadtree segment or region based fusion algorithms were performed using ecognition software, a commercially available remote sensing software suite, and used to classify the images. The Munechika fusion improved the spatial resolution for the images containing silver nanoparticles, while the segment fusion allowed classification and fusion based on the tissue types in the sample, suggesting potential pathways for the uptake of the silver nanoparticles.

Time of flight secondary ion mass spectrometry surface and in-depth study of degradation of nanosheet poly(L-lactic acid) films.

With the advent of novel fabrication technologies, free-standing poly(l-lactic acid) (PLLA) nanosheets have been shown to have enhanced performance over their micro- or macroscale equivalents as tissue engineering and drug delivery constructs. In the present research, the authors investigated the surface degradation behavior of PLLA films as a function of confinement to a quasi-two-dimensional structure, and the degradation behavior of nanoscale PLLA films as a function of the initial molecular weight and depth, using time-of-flight secondary ion mass spectrometry. The authors found that nanofilms exhibit less segregation of shorter chains to the surface than microfilms, due to the constrained geometries of these morphologies. It was also concluded that the degradation rate at the surface of nanofilms related to the inverse of the initial molecular weight, as is the case in bulk-scale systems.

Quantitative TOF-SIMS analysis of oligomeric degradation products at the surface of biodegradable poly(alpha-hydroxy acid)s.

This paper reports the development of a new method for quantification of the hydrolytic surface degradation kinetics of biodegradable poly(alpha-hydroxy acid)s using time-of-flight secondary ion mass spectrometry (TOF-SIMS). We report results from static SIMS spectra of a series of poly(alpha-hydroxy acid)s including poly(glycolic acid), poly(L-lactic acid), and random poly(D,L-lactic acid-co-glycolic acid) hydrolyzed in various buffer systems. The distribution of the most intense peak intensities of ions generated in high mass range of the spectrum reflects the intact degradation products (oligomeric hydrolysis products) of each biodegradable polymer. First, a detailed analysis of the oligomeric ions is given based on rearrangement of the intact hydrolysis products. The pattern of ions can distinguish both degradation-generated intact oligomers and their fragment ion peaks with a variety of combinations of each repeat unit. Then, the integration and summation of the area of all ion peaks with the same number of repeat units is proposed as a measurement that provides a more accurate MW average than the typically used method which counts only the most intense peak. The multiple ion summation method described in this paper would be practical in the improvement of quantitative TOF-SIMS studies as a better data reduction method, especially in the surface degradation kinetics of biodegradable polymers.

Evaluation of matrix-assisted laser desorption ionization mass spectrometry for studying the sec-butyllithium and n-butyllithium initiated ring-opening polymerization of hexamethylcyclotrisiloxane (D3).

Matrix assisted laser desorption ionization (MALDI) was used to study the organolithium initiated ring-opening polymerization of hexamethylcyclotrisiloxane (D3) in a mixed solvent system. The mass spectral peak intensities were monitored to determine the effects of polymerization time, initiator concentration, and reaction temperature on the formation of the mono, di, and trisiloxanolate initiator species and the extent of chain redistribution. The three initiator species were formed by reacting n-butyllithium and sec-butyllithium with D3 in nonpolar solvent. The mass spectral results showed that sec-butyllithium and n-butyllithium form different populations of initiator species under the same conditions and that the measured mass spectral peak intensities do not accurately represent the population of siloxanolate initiator species prior to propagation. The changes in peak intensities were attributed to chain redistribution.

Quantitative analysis of technical polymer mixtures by matrix assisted laser desorption/ionization time of flight mass spectrometry.

We report quantitative MALDI-TOF measurements for polydimethylsiloxane (PDMS) of two different molecular weights using the relative ratio of the signal intensities of integrated oligomer distributions for these two molecular weight distributions. By reporting the ratio of intensities of the integrals of two oligomer distributions, we assume that the ionization and desorption efficiencies, crystallization conditions and other factors affecting intensity are similar. Poly(methyl methacrylate) (PMMA-33,000) was mixed with PDMS samples to show whether the presence of another material might affect the desorption efficiency. Quantitative values for the number-average molecular weight (Mn), weight-average molecular weight (Mw) and polydispersities (D) were calculated using the oligomer distributions. The results show a linear relationship between the analyte concentrations and the signal intensities in the range from 1,000 Da to 10,000 Da, and the desorption efficiency of these two PDMS materials was the same even in the presence of PMMA.

Tailored delivery of active keratinocyte growth factor from biodegradable polymer formulations.

We report the results of a high throughput screening campaign that is aimed to develop a biodegradable polymer-based formulation to deliver active keratinocyte growth factor (KGF) and provide a means to tune the KGF delivery rate. A statistical design strategy was used to prepare and screen a series of polymer blends that were composed of poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and the surfactant sodium bis(ethylhexyl)sulfosuccinate (Aerosol-OT, AOT). Chloroform was the solvent. Our high throughput screening method used a two-tiered assessment strategy. At Level 1, we identified "lead" KFG-loaded formulations that exhibited KGF emission spectra that were the most similar to the native KGF spectrum recorded in buffer. At Level 2, we used steady-state emission and a homogeneous polarization immunoassay strategy to determine the concentration of total and active KGF, respectively, liberated from the lead formulations during biodegradation. After preparing and screening 2500 formulations, we identified several viable, lead formulations. An analysis of the data showed that the combination of PLA, PGA, and AOT were important to yield a high fraction of active KGF upon release from the formulation; no combination of any two together produced an effect as good as the ternary formulation. The optimum formulations that yielded the highest fraction of active KGF upon release had the following general features: PLA/PGA (w/w) near unity, AOT loading of 100-200 mM, water/AOT mole ratio of 10-20, and a pH between 6 and 8. PLA alone cast from chloroform delivered KGF, but that KGF did not bind to anti-KGF antibodies (i.e., it was inactive). We can tune the KGF release kinetics by more than two orders of magnitude while maintaining the KGF activity upon liberation from the formulation by adjusting the PLA molecular weight.

Interleukin-1 facilitates airway epithelial migration in response to injury.

OBJECTIVE: To test the hypothesis that interleukin (IL)-1 plays a permissive role in respiratory epithelial cell migration and proliferation. STUDY DESIGN: Primary cultures of porcine respiratory epithelial cells or tracheal organ explants were cultured in the presence or absence of function-blocking antibodies to IL-1. Areas of epithelial cell outgrowth were determined in control and antibody-treated organ explants daily for 4 days. At intervals, cultured cells were collected for cell counting and viability determination. Time course and dose-response curves were constructed for control and antibody-treated groups. RESULTS: Interleukin-1 secretion into culture supernatants increased sharply from days 3 to 7. Outgrowths from tracheal explants were reduced by greater than 60% by single antibody treatment, and by over 90% by treatment with antibodies to both IL-1alpha and -1beta by day 4 of culture. Function-blocking antibodies to IL-1 significantly reduced cell number by day 7 of culture. CONCLUSIONS: Interleukin-1 is produced by respiratory epithelial cells in culture during log phase growth and plays a permissive role in cell migration and proliferation.

Use of geostatistics for remediation planning to transcend urban political boundaries.

Soil remediation plans are often dictated by areas of jurisdiction or property lines instead of scientific information. This study exemplifies how geostatistically interpolated surfaces can substantially improve remediation planning. Ordinary kriging, ordinary co-kriging, and inverse distance weighting spatial interpolation methods were compared for analyzing surface and sub-surface soil sample data originally collected by the US EPA and researchers at the University at Buffalo in Hickory Woods, an industrial-residential neighborhood in Buffalo, NY, where both lead and arsenic contamination is present. Past clean-up efforts estimated contamination levels from point samples, but parcel and agency jurisdiction boundaries were used to define remediation sites, rather than geostatistical models estimating the spatial behavior of the contaminants in the soil. Residents were understandably dissatisfied with the arbitrariness of the remediation plan. In this study we show how geostatistical mapping and participatory assessment can make soil remediation scientifically defensible, socially acceptable, and economically feasible.

Characteristic fragmentation of polysiloxane monolayer films by bombardment with monatomic and polyatomic primary ions in TOF-SIMS.

This study reports the characteristic fragmentation patterns from two polysiloxane polymers that form ordered overlayer on silver substrates. Results are compared for the bombardment of various monatomic and polyatomic projectiles of Cs(+), C(60)(+) (10 keV), Bi(1)(+), and Bi(3)(+) (25 keV) in the high mass range time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra. Results are reported from sub-monolayer (solution cast) coverages of poly(dimethylsiloxane)s with the number average molecular weights (M(n)) of 2200 and 6140 Da, respectively, and Langmuir-Blodgett monolayers of poly(methylphenylsiloxane) with molecular weights (MW) from 600 and 1000 Da. For each film, Bi projectiles resulted in the emission of positive silver cluster ions from the substrate under the polymer overlayer and peaks corresponding to silver cluster ions with larger mass were observed by impact of polyatomic 25 keV Bi(3)(+) projectiles. In addition, depending on the change of energy of Bi (3) (+) , a different pattern of fragments was observed. With Cs(+) and C(60)(+) impact, however, the emission of silver cluster ions was not detected. In the case of C(60)(+) impact for PDMS-6140, peaks corresponding to silver-cationized intact oligomers were not observed. In this paper, these results are explained by the possible bombardment mechanism for each projectile, based on its mass, energy, and split trajectories of the component atoms under the polyatomic impact.

Determining the protein drug release characteristics and cell adhesion to a PLLA or PLGA biodegradable polymer membrane.

Biodegradable polymers are of interest for developing controlled protein drug delivery platforms. In this study, two poly (alpha-hydroxy) esters were formulated with Aerosol-OT, a surfactant stabilizer, to encapsulate the protein keratinocyte growth factor (KGF) for controlled release KGF is involved in a number of crucial biologic processes, most notably epithelial growth and repair. The concentration of KGF that caused a biological response in vitro was determined (optimally 10 ng/mL) and compared with the release of KGF from the two biodegradable polymer membrane formulations. Each polymer formulation released biologically relevant levels, 10 ng/mL of active KGF, although with different times release kinetics. The membrane composed of PLGA/AOT/KGF exhibited a faster release rate of KGF into solution after 120 h of degradation time than the release rate of the PLLA/AOT/KGF matrices. Cell seeding assays showed that both polymer matrices, when formulated with AOT, sustained cell growth. Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was used to characterize the distribution of AOT and KGF through the polymer membrane. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.