International journal of pharmaceutics, Jan 30, 2015
Isothermal titration calorimetry (ITC) was utilised to investigate suitability of the technique t... more Isothermal titration calorimetry (ITC) was utilised to investigate suitability of the technique to determine the stoichiometry and thermodynamics of the interactions that occur between a commonly used chemotherapeutic drug, namely doxorubicin, and a polymer bead-based drug delivery embolisation system (DC Bead™). Six temperatures were selected for drug-polymer titrations (293-313K) and in all cases an initially exothermic signal reverted to an endothermic response upon the saturation of the beads with drug. From these experiments, and subsequent calculations, the molar ratio of drug to SO3(-) (polymer) was found to be 0.4:1 at all temperatures studied. Enthalpic data was calculated from the raw ITC data with an average enthalpy of drug-polymer binding of - 14.8kJmol(-1) at 293K through to - 19.4kJmol(-1) at 313K implying the process is enthalpically-driven yet only affected by an increase in experimental temperature to a limited extent whereby an increase in experimental temperature...
Engraftment and survival of stem cells in the infarcted myocardium remain problematic in cell-bas... more Engraftment and survival of stem cells in the infarcted myocardium remain problematic in cell-based therapy for cardiovascular disease. To overcome these issues, encapsulated mesenchymal stem cells (eMSCs) were developed that were transfected to produce glucagon-like peptide-1, an incretin hormone with known cardioprotective effects, alongside MSC endogenous paracrine factors. This study was designed to investigate the efficacy of different doses of intracoronary infusion of eMSC in a porcine model of acute myocardial infarction (AMI). One hundred pigs were subjected to a moderate AMI (posterolateral AMI; n=50) or a severe AMI (anterior AMI; n=50), whereupon surviving animals (n=36 moderate, n=33 severe) were randomized to receive either intracoronary infusion of 3 incremental doses of eMSC or Ringers' lactate control. Cardiac function was assessed using invasive hemodynamics, echocardiography, and histological analysis. A trend was observed in the moderate AMI model, whereas in...
The DC Bead is fast becoming the product of choice for use in the treatment of intermediate-stage... more The DC Bead is fast becoming the product of choice for use in the treatment of intermediate-stage hepatocellular carcinoma. It is a drug-eluting embolization system that is delivered intra-arterially and combines the effects of physical occlusion of the blood supply to a tumor with the local controlled delivery of a chemotherapeutic agent. While not suitable for use with all drugs, the components of this device enable rapid loading and sustained elution of therapeutic amounts of a range of clinically relevant anticancer compounds. Extensive preclinical testing has demonstrated the reproducibility and reliability of the device, together with reduced systemic drug exposure and sustained local drug delivery. Moreover, these attributes are translating into the clinic as significant benefits to patients with many types of liver tumors.
Ion-exchange microspheres (IEMs) are widely employed in controlled drug delivery of ionic drugs d... more Ion-exchange microspheres (IEMs) are widely employed in controlled drug delivery of ionic drugs due to their high loading capacity and the possibility to obtain the controlled release of the loaded drug(s) at a specific site. Among IEMs, DC Bead(™) are embolic microdevices (100-300 μm diameter) designed for transarterial chemoembolization (TACE) and composed of cross-linked poly(vinyl alcohol) (PVA) hydrogel, bearing anionic sulfonate moieties on the cross-links, and able to bind cationic drugs such as doxorubicin hydrochloride (Dox). Even if DC Bead(™) were studied for their release and bulk characteristics, a thorough characterization of these devices is still lacking. In particular, the aim of this work was the determination of bound and free water, Dox distribution within the microdevices and drug-DC Bead(™) interactions, in terms of transport features within the device. Compared with previous results, different Dox radial distributions in DC Bead(™) were found, and related to bead microsctructure and ion exchange mechanism. Artifacts due to the self-quenching of Dox at high concentration were prevented and the diffusion coefficients of drug-polymer (Dox-ionic sites) evaluated in different sections of the microspheres. Furthermore, DSC results indicated that in the hydrogel either free (bulk) or bound (non-freezable) water could be found, and that no freezing-bound water was present.
Journal of Vascular and Interventional Radiology, 2015
To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [D... more To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo. An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model. Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology. A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.
Langmuir : the ACS journal of surfaces and colloids, Jan 11, 2015
We quantitatively determined interfacial potentials between cell-sized particles and stimulus-res... more We quantitatively determined interfacial potentials between cell-sized particles and stimulus-responsive hydrogels using a microinterferometer. The hydrogel is based on physically interconnected ABA triblock copolymer micelles comprising an inner biocompatible PMPC block and two outer pH-responsive PDPA blocks. The out-of-plane temporal fluctuation in the position of the cell-sized particles was calculated from changes in the interference pattern measured by Reflection Interference Contrast Microscopy (RICM), thus yielding the particle-substrate interaction potential V (Δh). Measurements in pH buffers ranging from 7.0 to 7.8 resulted in a systematic reduction in height of the potential minima ⟨Δh⟩ and a concomitant increase in the potential curvature V″ (Δh). The experimental data were analyzed by applying the modified Ross and Pincus model for polyelectrolytes, while accounting for gravitation, lubrication and van der Waals interactions. Elastic moduli calculated from V″ (Δh) were ...
Journal of Vascular and Interventional Radiology, 2015
To quantify changes in tumor microvascular (&... more To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. Rabbit Vx2 liver tumors were embolized with 100-300-μm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3-5 per group; 18 total). Mean microvascular density was 70 vessels/mm(2) ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31(+) structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy.
Journal of Vascular and Interventional Radiology, 2015
To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an ani... more To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an animal model of liver tumors. Inoculation of VX2 tumors in the left liver lobe was performed successfully in 12 New Zealand white rabbits weighing 3.7 kg ± 0.5 (mean ± SD). Tumors were deemed eligible for oxygen measurements when the maximum transverse diameter measured 15 mm or more by ultrasound examination. Direct monitoring of oxygenation of implanted rabbit hepatic VX2 tumors was performed with a fiberoptic electrode during and after transarterial embolization of the proper hepatic artery to angiographic flow stasis with microspheres measuring 70-150 μm, 100-300 μm, or 300-500 μm in diameter. Failure to achieve tumor hypoxia as defined despite angiographic flow stasis was observed in 10 of 11 animals. Embolization microsphere size effect failed to demonstrate a significant trend on hypoxia outcome among the diameters tested, and pair-wise comparisons of different embolic diameter treatment groups showed no difference in hypoxia outcome. All microsphere diameters tested resulted in similar absolute reduction (24.3 mm Hg ± 18.3, 29.1 mm Hg ± 1.8, and 19.9 mm Hg ± 9.3, P = .66) and percentage decrease in oxygen (56.0 mm Hg ± 23.9, 56.0 mm Hg ± 6.4, and 35.8 mm Hg ± 20.6, P = .65). Pair-wise comparisons for percent tumor area occupied by embolic agents showed a significantly reduced fraction for 300-500 μm diameters compared with 70-150 μm diameters (P < .05). In the rabbit VX2 liver tumor model, three tested microsphere diameters failed to cause tumor hypoxia as measured by a fiberoptic probe sensor according to the adopted hypoxia definitions.
Langmuir : the ACS journal of surfaces and colloids, Jan 11, 2005
Spectroscopic ellipsometry has been used to examine the pH-responsive interfacial adsorption of a... more Spectroscopic ellipsometry has been used to examine the pH-responsive interfacial adsorption of a series of biocompatible diblock copolymers incorporating 2-methacryloyloxyethyl phosphorylcholine-based (MPC) residues and 2-(dialkylamino)ethyl methacrylate residues, with a specific focus on 2-(diethylamino)ethyl groups (referred to as MPCm-DEAn, where m and n refer to the mean degrees of polymerization of each block) at the hydrophilic silicon oxide/water interface. For all the copolymers studied the surface excess shows only weak concentration dependence. Increasing the length of the DEA block has little effect on the dynamic or equilibrated adsorption at pH 7, indicating that the DEA block adopts a flat conformation on the silicon oxide surface at this pH. With increasing pH, however, the surface excess shows a dramatic increase, followed by a subsequent decline. The observed maximum in surface excess represents a balance between charge over-compensation of the copolymer with the o...
A well-defined, double-hydrophilic diblock copolymer comprising poly[2-(methacryloyloxy)ethyl pho... more A well-defined, double-hydrophilic diblock copolymer comprising poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-(glycerol monomethacrylate) (PMPC30-PGMA30, where the numbers represent the average degrees of polymerization for each block) was evaluated for the synthesis of colloidally stable ultrafine magnetite sols. Sterically stabilized paramagnetic sols were prepared in aqueous solution by chemical coprecipitation of ferric and ferrous salts in the presence of this block copolymer. The PMPC30-PGMA30-stabilized magnetite sol had a mean transmission electron microscopy (TEM) diameter of 9.4 +/- 1.7 nm and a mean hydrodynamic diameter of 34 nm. This sol exhibited improved colloidal stability with respect to long-term storage and pH variation compared with magnetite sols prepared in the presence of alternative water-soluble homopolymers and diblock copolymers. Fourier transform infrared (FT-IR) spectroscopy, thermogravimetry, electron spectroscopy imaging (ESI), and zeta potential studies indicate that the PMPC30-PGMA30 diblock copolymer was adsorbed onto the surface of the sol via the PGMA30 block, with the PMPC30 chains acting as the stabilizing block. Such sterically stabilized sols are expected to be improved contrast agents for magnetic resonance imaging (MRI) applications.
Surface-initiated atom transfer radical polymerization (SI-ATRP) has been used to grow brushes of... more Surface-initiated atom transfer radical polymerization (SI-ATRP) has been used to grow brushes of poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) from silicon wafers using a polyelectrolytic macroinitiator on planar silicon wafers. Film thicknesses of up to 450 nm were possible within 21 h, and the effect of adding activator and deactivator species on the brush growth rate was studied. The solvation of PMPC brushes in mixed alcohol/water solvents was investigated using in situ ellipsometry. Co-nonsolvency (a re-entrant swelling transition) behavior was observed in water/ethanol binary mixtures; that is, the PMPC brushes were highly swollen in either pure ethanol or water but became deswollen at specific ethanol-rich solvent compositions. A similar effect was obtained with water/2-propanol mixtures, except that in this case pure 2-propanol was not a particularly good solvent for the PMPC chains. However, co-nonsolvency was not observed for water/methanol binary mixtures, since the brushes remained well swollen at all solvent compositions. This is consistent with prior reports of co-nonsolvency effects in both PMPC gels and linear PMPC chains. However, this is the first report of this phenomenon for PMPC brushes and one of the first examples of co-nonsolvency observed for any polymer brush system. A direct comparison of brush and gel swelling reveals an approximate power-law relationship between the equilibrium volumes of these two systems at various solvent compositions, which is interpreted by treating the brush layer as a surface-attached gel. We believe this to be the first quantitative comparison of brush and gel swelling using the same polymer under the same conditions. The kinetics of the PMPC brush response to adjustment of the alcohol/water composition is relatively fast, with the brush volume change occurring on time scales of less than 1 min as judged by in situ ellipsometry.
... Department of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom. Yinghua Ma,Xavie... more ... Department of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom. Yinghua Ma,Xavier Bories-Azeau, and Steven P ... Stacey E. Kirkland, Ryan M. Hensarling, Shawn D. McConaughy, Yanlin Guo, William L. Jarrett and Charles L. McCormick. Biomacromolecules ...
International journal of pharmaceutics, Jan 30, 2015
Isothermal titration calorimetry (ITC) was utilised to investigate suitability of the technique t... more Isothermal titration calorimetry (ITC) was utilised to investigate suitability of the technique to determine the stoichiometry and thermodynamics of the interactions that occur between a commonly used chemotherapeutic drug, namely doxorubicin, and a polymer bead-based drug delivery embolisation system (DC Bead™). Six temperatures were selected for drug-polymer titrations (293-313K) and in all cases an initially exothermic signal reverted to an endothermic response upon the saturation of the beads with drug. From these experiments, and subsequent calculations, the molar ratio of drug to SO3(-) (polymer) was found to be 0.4:1 at all temperatures studied. Enthalpic data was calculated from the raw ITC data with an average enthalpy of drug-polymer binding of - 14.8kJmol(-1) at 293K through to - 19.4kJmol(-1) at 313K implying the process is enthalpically-driven yet only affected by an increase in experimental temperature to a limited extent whereby an increase in experimental temperature...
Engraftment and survival of stem cells in the infarcted myocardium remain problematic in cell-bas... more Engraftment and survival of stem cells in the infarcted myocardium remain problematic in cell-based therapy for cardiovascular disease. To overcome these issues, encapsulated mesenchymal stem cells (eMSCs) were developed that were transfected to produce glucagon-like peptide-1, an incretin hormone with known cardioprotective effects, alongside MSC endogenous paracrine factors. This study was designed to investigate the efficacy of different doses of intracoronary infusion of eMSC in a porcine model of acute myocardial infarction (AMI). One hundred pigs were subjected to a moderate AMI (posterolateral AMI; n=50) or a severe AMI (anterior AMI; n=50), whereupon surviving animals (n=36 moderate, n=33 severe) were randomized to receive either intracoronary infusion of 3 incremental doses of eMSC or Ringers' lactate control. Cardiac function was assessed using invasive hemodynamics, echocardiography, and histological analysis. A trend was observed in the moderate AMI model, whereas in...
The DC Bead is fast becoming the product of choice for use in the treatment of intermediate-stage... more The DC Bead is fast becoming the product of choice for use in the treatment of intermediate-stage hepatocellular carcinoma. It is a drug-eluting embolization system that is delivered intra-arterially and combines the effects of physical occlusion of the blood supply to a tumor with the local controlled delivery of a chemotherapeutic agent. While not suitable for use with all drugs, the components of this device enable rapid loading and sustained elution of therapeutic amounts of a range of clinically relevant anticancer compounds. Extensive preclinical testing has demonstrated the reproducibility and reliability of the device, together with reduced systemic drug exposure and sustained local drug delivery. Moreover, these attributes are translating into the clinic as significant benefits to patients with many types of liver tumors.
Ion-exchange microspheres (IEMs) are widely employed in controlled drug delivery of ionic drugs d... more Ion-exchange microspheres (IEMs) are widely employed in controlled drug delivery of ionic drugs due to their high loading capacity and the possibility to obtain the controlled release of the loaded drug(s) at a specific site. Among IEMs, DC Bead(™) are embolic microdevices (100-300 μm diameter) designed for transarterial chemoembolization (TACE) and composed of cross-linked poly(vinyl alcohol) (PVA) hydrogel, bearing anionic sulfonate moieties on the cross-links, and able to bind cationic drugs such as doxorubicin hydrochloride (Dox). Even if DC Bead(™) were studied for their release and bulk characteristics, a thorough characterization of these devices is still lacking. In particular, the aim of this work was the determination of bound and free water, Dox distribution within the microdevices and drug-DC Bead(™) interactions, in terms of transport features within the device. Compared with previous results, different Dox radial distributions in DC Bead(™) were found, and related to bead microsctructure and ion exchange mechanism. Artifacts due to the self-quenching of Dox at high concentration were prevented and the diffusion coefficients of drug-polymer (Dox-ionic sites) evaluated in different sections of the microspheres. Furthermore, DSC results indicated that in the hydrogel either free (bulk) or bound (non-freezable) water could be found, and that no freezing-bound water was present.
Journal of Vascular and Interventional Radiology, 2015
To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [D... more To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo. An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model. Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology. A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.
Langmuir : the ACS journal of surfaces and colloids, Jan 11, 2015
We quantitatively determined interfacial potentials between cell-sized particles and stimulus-res... more We quantitatively determined interfacial potentials between cell-sized particles and stimulus-responsive hydrogels using a microinterferometer. The hydrogel is based on physically interconnected ABA triblock copolymer micelles comprising an inner biocompatible PMPC block and two outer pH-responsive PDPA blocks. The out-of-plane temporal fluctuation in the position of the cell-sized particles was calculated from changes in the interference pattern measured by Reflection Interference Contrast Microscopy (RICM), thus yielding the particle-substrate interaction potential V (Δh). Measurements in pH buffers ranging from 7.0 to 7.8 resulted in a systematic reduction in height of the potential minima ⟨Δh⟩ and a concomitant increase in the potential curvature V″ (Δh). The experimental data were analyzed by applying the modified Ross and Pincus model for polyelectrolytes, while accounting for gravitation, lubrication and van der Waals interactions. Elastic moduli calculated from V″ (Δh) were ...
Journal of Vascular and Interventional Radiology, 2015
To quantify changes in tumor microvascular (&... more To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. Rabbit Vx2 liver tumors were embolized with 100-300-μm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3-5 per group; 18 total). Mean microvascular density was 70 vessels/mm(2) ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31(+) structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy.
Journal of Vascular and Interventional Radiology, 2015
To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an ani... more To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an animal model of liver tumors. Inoculation of VX2 tumors in the left liver lobe was performed successfully in 12 New Zealand white rabbits weighing 3.7 kg ± 0.5 (mean ± SD). Tumors were deemed eligible for oxygen measurements when the maximum transverse diameter measured 15 mm or more by ultrasound examination. Direct monitoring of oxygenation of implanted rabbit hepatic VX2 tumors was performed with a fiberoptic electrode during and after transarterial embolization of the proper hepatic artery to angiographic flow stasis with microspheres measuring 70-150 μm, 100-300 μm, or 300-500 μm in diameter. Failure to achieve tumor hypoxia as defined despite angiographic flow stasis was observed in 10 of 11 animals. Embolization microsphere size effect failed to demonstrate a significant trend on hypoxia outcome among the diameters tested, and pair-wise comparisons of different embolic diameter treatment groups showed no difference in hypoxia outcome. All microsphere diameters tested resulted in similar absolute reduction (24.3 mm Hg ± 18.3, 29.1 mm Hg ± 1.8, and 19.9 mm Hg ± 9.3, P = .66) and percentage decrease in oxygen (56.0 mm Hg ± 23.9, 56.0 mm Hg ± 6.4, and 35.8 mm Hg ± 20.6, P = .65). Pair-wise comparisons for percent tumor area occupied by embolic agents showed a significantly reduced fraction for 300-500 μm diameters compared with 70-150 μm diameters (P < .05). In the rabbit VX2 liver tumor model, three tested microsphere diameters failed to cause tumor hypoxia as measured by a fiberoptic probe sensor according to the adopted hypoxia definitions.
Langmuir : the ACS journal of surfaces and colloids, Jan 11, 2005
Spectroscopic ellipsometry has been used to examine the pH-responsive interfacial adsorption of a... more Spectroscopic ellipsometry has been used to examine the pH-responsive interfacial adsorption of a series of biocompatible diblock copolymers incorporating 2-methacryloyloxyethyl phosphorylcholine-based (MPC) residues and 2-(dialkylamino)ethyl methacrylate residues, with a specific focus on 2-(diethylamino)ethyl groups (referred to as MPCm-DEAn, where m and n refer to the mean degrees of polymerization of each block) at the hydrophilic silicon oxide/water interface. For all the copolymers studied the surface excess shows only weak concentration dependence. Increasing the length of the DEA block has little effect on the dynamic or equilibrated adsorption at pH 7, indicating that the DEA block adopts a flat conformation on the silicon oxide surface at this pH. With increasing pH, however, the surface excess shows a dramatic increase, followed by a subsequent decline. The observed maximum in surface excess represents a balance between charge over-compensation of the copolymer with the o...
A well-defined, double-hydrophilic diblock copolymer comprising poly[2-(methacryloyloxy)ethyl pho... more A well-defined, double-hydrophilic diblock copolymer comprising poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-(glycerol monomethacrylate) (PMPC30-PGMA30, where the numbers represent the average degrees of polymerization for each block) was evaluated for the synthesis of colloidally stable ultrafine magnetite sols. Sterically stabilized paramagnetic sols were prepared in aqueous solution by chemical coprecipitation of ferric and ferrous salts in the presence of this block copolymer. The PMPC30-PGMA30-stabilized magnetite sol had a mean transmission electron microscopy (TEM) diameter of 9.4 +/- 1.7 nm and a mean hydrodynamic diameter of 34 nm. This sol exhibited improved colloidal stability with respect to long-term storage and pH variation compared with magnetite sols prepared in the presence of alternative water-soluble homopolymers and diblock copolymers. Fourier transform infrared (FT-IR) spectroscopy, thermogravimetry, electron spectroscopy imaging (ESI), and zeta potential studies indicate that the PMPC30-PGMA30 diblock copolymer was adsorbed onto the surface of the sol via the PGMA30 block, with the PMPC30 chains acting as the stabilizing block. Such sterically stabilized sols are expected to be improved contrast agents for magnetic resonance imaging (MRI) applications.
Surface-initiated atom transfer radical polymerization (SI-ATRP) has been used to grow brushes of... more Surface-initiated atom transfer radical polymerization (SI-ATRP) has been used to grow brushes of poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) from silicon wafers using a polyelectrolytic macroinitiator on planar silicon wafers. Film thicknesses of up to 450 nm were possible within 21 h, and the effect of adding activator and deactivator species on the brush growth rate was studied. The solvation of PMPC brushes in mixed alcohol/water solvents was investigated using in situ ellipsometry. Co-nonsolvency (a re-entrant swelling transition) behavior was observed in water/ethanol binary mixtures; that is, the PMPC brushes were highly swollen in either pure ethanol or water but became deswollen at specific ethanol-rich solvent compositions. A similar effect was obtained with water/2-propanol mixtures, except that in this case pure 2-propanol was not a particularly good solvent for the PMPC chains. However, co-nonsolvency was not observed for water/methanol binary mixtures, since the brushes remained well swollen at all solvent compositions. This is consistent with prior reports of co-nonsolvency effects in both PMPC gels and linear PMPC chains. However, this is the first report of this phenomenon for PMPC brushes and one of the first examples of co-nonsolvency observed for any polymer brush system. A direct comparison of brush and gel swelling reveals an approximate power-law relationship between the equilibrium volumes of these two systems at various solvent compositions, which is interpreted by treating the brush layer as a surface-attached gel. We believe this to be the first quantitative comparison of brush and gel swelling using the same polymer under the same conditions. The kinetics of the PMPC brush response to adjustment of the alcohol/water composition is relatively fast, with the brush volume change occurring on time scales of less than 1 min as judged by in situ ellipsometry.
... Department of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom. Yinghua Ma,Xavie... more ... Department of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom. Yinghua Ma,Xavier Bories-Azeau, and Steven P ... Stacey E. Kirkland, Ryan M. Hensarling, Shawn D. McConaughy, Yanlin Guo, William L. Jarrett and Charles L. McCormick. Biomacromolecules ...
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Papers by Andrew L Lewis