UMLS:C0267964 - FACTA Search

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Query: UMLS:C0267964 (PAA)
2,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conjugation of proteins to copolymers from poly(acrylic acid) grafted onto PEO-PPO-PEO backbone (Pluronic-PAA) following adsorption of the conjugates onto hydrophobic surfaces is reported. Insulin-Pluronic-PAA conjugates show negligible internalization of insulin into human uterine smooth muscle cells as well as enhancement of mitogenic activity. Glucose-induced release of glycated albumin complexed with a Pluronic-PAA-concanavalin conjugate and adsorbed onto polystyrene nanospheres may provide a model for a glucose-responsive protein delivery system or a heterogeneous diagnostic device.
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PMID:Bioactive surfaces via immobilization of self-assembling polymers onto hydrophobic materials. 1041 66

The capability of a family of copolymers comprising Pluronic (PEO-PPO-PEO) surfactants covalently conjugated with poly(acrylic acid) (Pluronic-PAA) to enhance the aqueous solubility and stability of the lactone form of camptothecin (CPT) was studied. The unprotected lactone form of CPT, which possesses cytotoxic activity, is rapidly converted to the ring-opened carboxylate form under physiological conditions. Firstly, surfactant properties such as critical micellization concentration (CMC) of Pluronic-PAA copolymers were characterized. Then, the equilibrium solubility partitioning and hydrolysis of the lactone form of CPT in the presence of Pluronic-PAA in water and in human serum were analyzed. CPT solubility in polymer micellar solutions was ca. 3- to 4-fold higher than that in water at pH 5. The amount of CPT solubilized per PPO was considerably greater in the Pluronic-PAA solutions than in the parent Pluronic solution, which suggests that the drug is not only solubilized by the hydrophobic cores and also by the hydrophilic POE-PAA shells of the micelles. The equilibrium partition coefficient of the CPT lactone between Pluronic-PAA solutions and water exceeded (2-3) x 10(3). The complete solubilization of CPT and the absence of chemical interactions between CPT and Pluronic-PAA were confirmed by modulated temperature differential scanning calorimetry (MTDSC), infrared spectroscopy, and X-ray diffraction of films. The loading of CPT into the Pluronic-PAA micelles was able to prevent the hydrolysis of the lactone group of the drug for 2 h at pH 8 in water. When compared to the unprotected CPT, the kinetics of the CPT hydrolysis in human serum was about 10-fold slower in the Pluronic-PAA formulations.
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PMID:Solubilization and stabilization of camptothecin in micellar solutions of pluronic-g-poly(acrylic acid) copolymers. 1521 85

Transient rheological properties and mucoadhesion of hydrogels composed of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO, or Pluronic) block copolymers and poly(acrylic acid) were explored. Nine Pluronic copolymers ranging in nominal molecular weight and PPO/PEO content were grafted to PAA through C-C bonds, with or without the use of divinyl cross-linker, ethylene glycol dimethacrylate (EGDMA). The hydrogel elasticity increased with the PPO content in the copolymers, as well as in the presence of EGDMA. Tensile tests were conducted to measure the fracture strength and the work of adhesion between the hydrogels and rat intestinal tissue. The fracture strength was proportional to the gel pseudoequilibrium modulus and depended on the nominal length of the PPO segments in the parent Pluronic copolymer. The work of mucoadhesion and gel cohesion declined with the loss angle measured in oscillatory shear experiments. The length of the PEO segments in Pluronic affected the work of adhesion. Applications of the Pluronic-PAA gels as vehicles in oral drug delivery are discussed. The longest Pluronic copolymers bonded to PAA resulted in copolymeric gels with strongest mucoadhesive properties.
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PMID:Bioadhesive properties and rheology of polyether-modified poly(acrylic acid) hydrogels. 1533 81

Pluronic-PAA, a thermogelling copolymer composed of side chains of poly(acrylic acid) (PAA) grafted onto a backbone of Pluronic copolymer, is of interest as a vehicle for the controlled release of compounds. An important feature of such a vehicle is its bioadhesive/mucoadhesive properties, which in the case of Pluronic-PAA are significant due to the presence of the PAA side chains. An atomic force microscopy (AFM) method has been developed and utilized to investigate the interactions between a Pluronic-PAA-modified microsphere and mucous substrates. The bioadhesive force was successfully measured, and trends were observed under conditions of varying pH and ionic strength. Pluronic-PAA exhibits significant mucoadhesion over a range of pH values, with mucoadhesion being optimal at pH 4-5 (adhesive force approximately 80 mN/cm(2)) and dropping sharply at higher pH, to a value of approximately 20 mN/cm(2) at pH 8. The mucoadhesive force decreased with increasing ionic strength, from a value of approximately 80 mN/cm(2) in 0.025 M NaCl to approximately 25 mN/cm(2) in 1.0 M NaCl. These results have been interpreted in terms of the effect of changing pH and ionic strength on electrostatic interactions and swelling of the polymer and mucin layers. Tensiometric force measurements indicated that hydrophobic interactions, as well as hydrogen bonding and electrostatic interactions, were significant in the mucoadhesion of Pluronic-PAA copolymers. Experiments with a range of Pluronic-PAA copolymers with varying PPO contents in the Pluronic segments showed that increasing the overall PPO content increased the hydrophobicity of the polymer solutions. This was reflected in the increases in the advancing contact angles with the mucin layer, indicating that hydrophobic interactions play a role in the adhesion of Pluronic-PAA to mucin.
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PMID:Adhesion of polyether-modified poly(acrylic acid) to mucin. 1549 Dec 11

Potential utility of copolymers comprising Pluronic (PEO-PPO-PEO) surfactants covalently conjugated with poly(acrylic acid) (PAA) as excipients for sustained-release tablets was explored. Apparent particle density, particle size distribution, Carr index, thermal stability, and compression behavior of the Pluronic-PAA copolymers were characterized. Tablets prepared by direct compression of blends of Pluronic-PAA copolymers were evaluated on the basis of their thermomechanical profile, crushing strength, friability, and drug release properties. Small molecular weight drugs of aqueous solubility decreasing in the order theophylline>hydrochlorothiazide>nitrofurantoin were incorporated to the tablets. For comparison purposes, tablets were also prepared from PAA of Carbopol 71G (C71G), and mixtures of C71G and Pluronic F127, with each of the above three drugs. The Pluronic-PAA aggregates are stabilized by hydrophobic associations between poly(propylene oxide) (PPO) segments in aqueous solutions, and thus require higher ionization of the carboxylic groups to overcome the associations and swell. The swelling pattern of the Pluronic-PAA copolymers is more dramatically pH-dependent than that of Carbopol lacking any hydrophobic associations. The drug retention in and release from the Pluronic-PAA based tablets is profoundly pH-dependent and hence specific to the pH exceeding that of the pK(a)>5 of these copolymers. Theophylline- and hydrochlorotiazide-containing tablets made with Pluronic-PAA copolymers showed a reduced release rate under acidic conditions compared to the neutral or alkaline conditions, while the opposite pattern was observed with the Carbopol-based tablets due to the different pH-dependent swelling behavior of the polymers. Nitrofurantoin-containing tablets showed a remarkably low drug release rate owing to the strong hydrophobic character of nitrofurantoin and of its complexes with the copolymers. Integrity of the nitrofurantoin-containing tablets was maintained during the 24h release test. Zero-order kinetics of the cumulative release profile of all drugs under study was observed with the Pluronic-PAA as a tablet excipient. Adequate mechanical properties, the self-assembling behavior, and the pH-sensitiveness of the Pluronic-PAA copolymers make them promising excipients for tablets with preferential delivery into a neutral to alkaline pH environment.
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PMID:Pluronic-g-poly(acrylic acid) copolymers as novel excipients for site specific, sustained release tablets. 1616 45

The temperature-induced structural changes and thermodynamics of ionic microgels based on poly(acrylic acid) (PAA) networks bonded with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) (Pluronic) copolymers have been studied by small-angle neutron scattering (SANS), ultra-small-angle neutron scattering (USANS), differential scanning calorimetry (DSC), and equilibrium swelling techniques. Aggregation within microgels based on PAA and either the hydrophobic Pluronic L92 (average composition, EO8PO52EO8; PPO content, 80%) or the hydrophilic Pluronic F127 (average composition, EO99PO67EO99; PPO content, 30%) was studied and compared to that in the solutions of the parent Pluronic. The neutron scattering results indicate the formation of micelle-like aggregates within the F127-based microgel particles, while the L92-based microgels formed fractal structures of dense nanoparticles. The microgels exhibit thermodynamically favorable volume phase transitions within certain temperature ranges due to reversible aggregation of the PPO chains, which occurs because of hydrophobic associations. The values of the apparent standard enthalpy of aggregation in the microgel suspensions indicate aggregation of hydrophobic clusters that are more hydrophobic than the un-cross-linked PPO chains in the Pluronic. Differences in the PPO content in Pluronics L92 and F127 result in a higher hydrophobicity of the resulting L92-PAA-EGDMAmicrogels and a larger presence of hydrophobic, densely cross-linked clusters that aggregate into supramolecular structures rather than micelle-like aggregates such as those formed in the F127-PAA-EGDMA microgels.
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PMID:Thermodynamics of temperature-sensitive polyether-modified poly(acrylic acid) microgels. 1645 80

Oral administration of anticancer agents is preferred by patients for its convenience and potential for use in outpatient and palliative setting. In addition, oral administration facilitates a prolonged exposure to the cytotoxic agents. Enhancement of bioavailability of emerging cytotoxic agents is a pre-requisite for successful development of oral modes of cancer treatment. Over the last decade, our studies have focused specifically on the utilization of large (MW>10(5)) and non-degradable polymers in oral chemotherapy. A family of block-graft copolymers of the poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) Pluronic(R) polyethers and poly(acrylic acid) (PAA) bound by carbon-carbon bonds emerged, wherein both polymeric components are generally recognized as safe. Animal studies with Pluronic-PAA copolymers demonstrated that these molecules are excreted when administered orally and do not absorb into the systemic circulation. The Pluronic-PAA copolymers are surface-active and self-assemble, at physiological pH, into intra- and intermolecular micelles with hydrophobic cores of dehydrated PPO and multilayered coronas of hydrophilic PEO and partially ionized PAA segments. These micelles efficiently solubilize hydrophobic drugs such as paclitaxel and steroids and protect molecules such as camptothecins from the hydrolytic reactions. High surface activity of the Pluronic-PAA copolymers in water results in interactions with cell membranes and suppression of the membrane pumps such as P-glycoprotein. The ionizable carboxyls in the micellar corona facilitate mucoadhesion that enhances the residence time of the micelles and solubilized drugs in the gastrointestinal tract. Large payloads of the Pluronic-PAA micelles with weakly basic and water-soluble drugs such as doxorubicin and its analogs, mitomycin C, mitoxantrone, fluorouracil, and cyclophosphamide are achieved through electrostatic interactions with the micellar corona. Mechanical and physical properties of the Pluronic-PAA powders, blends, and micelles allow for formulation procedures where an active is simply dispersed into an aqueous Pluronic-PAA micellar formulation followed by optional lyophilization and processing into a ready dosage form. We review a number of in vivo and in vitro experiments demonstrating that that the oral administration of the cytotoxics formulated with the Pluronic-PAA copolymer micelles results in enhanced drug bioavailability.
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PMID:Polymeric micelles in oral chemotherapy. 1832 19

The association between a randomly pyrene labeled PAA polymer (PAAMePy55) and a PEO-PPO-PEO triblock copolymer (P123) in aqueous solutions of different NaCl concentrations and pHs has been studied by means of dynamic light scattering (DLS) and steady-state fluorescence spectroscopy at 40 degrees C. At acidic pH values, in the low P123/PAAMePy55 molar ratio regime (i.e., at low P123 concentrations), the relaxation time distributions retrieved from the DLS data analysis were monomodal and very similar to those obtained for the pure PAAMePy55 solution. The apparent hydrodynamic radius of PAAMePy55 at low pH is 18 nm. At higher molar ratios (i.e., at high P123 concentrations), still in the acidic pH regime, bimodal relaxation time distributions were obtained, where the fast relaxation mode is connected to the translational diffusion of free P123 micelles with a hydrodynamic radius obtained at infinite P123 dilution (R(H,P123=0)) of 10-11 nm. This value coincides perfectly with the hydrodynamic radius of the pure P123 micelles at 40 degrees C, which was found to be ca. 10 nm at all pH values. The second mode corresponds to a complex consisting of one PAAMePy55 polymer chain and about 42 P123 micelles and with a R(H,P123=0) between 35 and 36 nm depending on pH. At pH 9, the mixed system also presented bimodal relaxation time distributions. At this high pH, the intermolecular association between PAAMePy55 and P123 is less strong than at acidic pH according to the steady-state fluorescence measurements. The fast mode is also in this case attributed to free P123 micelles whereas the second mode is related to the so-called "slow mode" commonly observed for polyelectrolyte solutions. In this system, it is related to the formation of multichain domains, that is, large domains formed by several PAAMePy55 chains that move in a common electrostatic field (i.e., a structure factor effect). The presence of P123 micelles does not lead to the total disruption of these domains. They may either contain entrapped P123 micelles or hydrophilic diblock impurities (originating from the P123 sample) that associate with the PAAMePy55 chains.
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PMID:Complex formation between a fluorescently-labeled polyelectrolyte and a triblock copolymer. 1935 71

By using absorption and fluorescence (steady-state and time-resolved) techniques, the interaction between a poly(acrylic acid) (PAA), randomly grafted with pyrene (Py) units (PAAMePy55), and a triblock copolymer of poly(ethylene oxide) and poly(propylene oxide) (EO(20)PO(68)EO(20), P123) was investigated. From the fluorescence data, it is shown that upon addition of P123 a decrease of the (pyrene-pyrene, Py-Py) intramolecular association, i.e., a decrease of dynamic and static excimer formation, is observed. Time-resolved fluorescence data reveal the existence of two types of monomers (monomers that are able to form excimer, MAGRE, and isolated monomers) and two excimers. Addition of P123 causes also an increase of the amount of isolated Py monomers. The overall fluorescence data suggest that the PAAMePy55 and the P123 block copolymer associate strongly at low pH, leading to the formation of P123 micelles surrounded by one PAAMePy55 chain, where the pyrene groups are located at the PPO/PEO interface of the P123 micelles. Steady-state fluorescence results also showed that an excess of P123 micelles in solution is required for the association to occur. At high pH (pH 9 and above) the situation is less clear. The steady-state (particularly in the I(1)/I(3) ratio) and time-resolved fluorescence results indicate a contact between the pyrene groups and PEO, which then would imply that there may be an interaction, but much weaker than at low pH.
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PMID:Association of a hydrophobically modified polyelectrolyte and a block copolymer followed by fluorescence techniques. 1935 73

Formation and stabilization of multiresponsive micelles with a mixed poly(ethylene oxide)/polyelectrolyte shell and a temperature-responsive poly(propylene oxide) core were studied. Various poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers were mixed with poly(acrylic acid)-block-poly(propylene oxide)-block-poly(acrylic acid) (PAA-PPO-PAA) or poly(dimethylaminoethyl methacrylate)-block-poly(propylene oxide)-block-poly(dimethylaminoethyl methacrylate) (PDMAEMA-PPO-PDMAEMA) triblock copolymers. The micelles formed by binary mixtures of well-defined compositions at a specific pH were additionally stabilized by loading with pentaerythritol tetraacrylate (PETA), that was polymerized and cross-linked "in situ" with UV assistance. Depending on both the composition of the copolymers and the experimental conditions, either spherical or wormlike "stabilized polymeric micelles with a mixed shell" (SPMMS) were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The SPMMS that contained PAA blocks in the shell were pH-sensitive, such that a reversible transition from well-dispersed SPMMS to precipitate could be promoted. In contrast, the SPMMS with a PEO/PDMAEMA mixed shell remained well-dispersed in the 2-11 pH range. Finally, SPMMS were successfully exploited as templates for the preparation of Ag nanoparticles (Ag NPs).
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PMID:Stabilized mixed micelles with a temperature-responsive core and a functional shell. 1940 18

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