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At least 1,243 records · Page 69Linked to original sources
PubMed1999

Preparation and characterization of polymer micelles from poly(ethylene glycol)-poly(D,L-lactide) block copolymers as potential drug carrier.

Poly(ethylene glycol)-poly(D,L-lactide) block copolymers (PEG-PLA) with varying composition were prepared through successive ring-opening polymerization of ethylene oxide and D,L-lactide using an anionic initiator, and their property of multimolecular micellization in aqueous milieu was examined in detail from the standpoint of designing carriers for hydrophobic drugs. The heterogeneity of PEG-PLA was found to crucially affect the size and distribution of micelles, and narrowly-distributed micelles with sizes of approximately 30 nm in diameter were formed only from PEG-PLA with a substantially narrow molecular weight distribution and an appropriate balance in the length ratio of the PEG and PLA segments in PEG-PLA, indicating the importance of establishing a reliable synthetic route for the block copolymers. PEG-PLA micelles have a considerably low critical association concentration (approximately 1.0 mg/l) which is apparently an advantage in utilizing these micelles as drug carriers in an extremely diluted condition.

Biocompatible Materials↗
PubMed2000

Doxorubicin-loaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance.

Doxorubicin (DOX) was physically loaded into micelles prepared from poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) block copolymer (PEG-PBLA) by an o/w emulsion method with a substantial drug loading level (15 to 20 w/w%). DOX-loaded micelles were narrowly distributed in size with diameters of approximately 50-70 nm. Dimer derivatives of DOX as well as DOX itself were revealed to be entrapped in the micelle, the former seems to improve micelle stability due to its low water solubility and possible interaction with benzyl residues of PBLA segments through pi-pi stacking. Release of DOX compounds from the micelles proceeded in two stages: an initial rapid release was followed by a stage of slow and long-lasting release of DOX. Acceleration of DOX release can be obtained by lowering the surrounding pH from 7.4 to 5.0, suggesting a pH-sensitive release of DOX from the micelles. A remarkable improvement in blood circulation of DOX was achieved by use of PEG-PBLA micelle as a carrier presumably due to the reduced reticuloendothelial system uptake of the micelles through a steric stabilization mechanism. Finally, DOX loaded in the micelle showed a considerably higher antitumor activity compared to free DOX against mouse C26 tumor by i.v. injection, indicating a promising feature for PEG-PBLA micelle as a long-circulating carrier system useful in modulated drug delivery.

Adenosarcoma↗
PubMed2000

Drug release from poly(acrylic acid) grafted poly(vinylidene fluoride) membrane bags in the gastrointestinal tract in the rat and dog.

Stomach-specific drug delivery systems would be of value in treating diseases of the upper gastrointestinal tract. The present study measured in vitro and in vivo drug release from pH-sensitive membrane bags, constructed of poly(acrylic acid) grafted onto a poly(vinylidene fluoride) (PAA-PVDF) membrane, which might be suitable for stomach-specific drug delivery. The used model drugs were propranolol-HCl (1.0 mg) and FITC-dextran MW 4400 (1.0 mg). Drug release in vivo was studied by inserting membrane bags into the stomach and proximal duodenum of anesthetized rats and dogs. At 30 and 180 min, the bags were removed from the lumens and residual drug content was determined. The release of either propranolol or FITC-dextran were comparable in both stomach and duodenum, showing that in vivo drug release did not depend on environmental pH. In vitro results suggested that these results could be explained by interactions between PAA and the mucous layers of the stomach and duodenum.

Acrylic Resins↗
PubMed2002

Poly(ethylene oxide)-block-poly(L-amino acid) micelles for drug delivery.

Block copolymer micelles encapsulate water insoluble drugs by chemical and physical means, and they may target therapeutics to their site of action in a passive or active way. In this review, we focus on micelles self-assembled from poly(ethylene oxide)-block-poly(L-amino acid) (PEO-b-PLAA). A common theme in these studies is the chemical modification of the core-forming PLAA block used to adjust and optimize the properties of PEO-b-PLAA micelles for drug delivery. Micelle-forming block copolymer-drug conjugates, micellar nanocontainers and polyion complex micelles have been obtained that mimic functional aspects of biological carriers, namely, lipoproteins and viruses. PEO-b-PLAA micelles may be advantageous in terms of safety, stability, and scale-up.

Animals↗
PubMed1997

Free energy of the binding of uridylic acid oligomers with double stranded poly(A) x poly(U).

The binding parameters (K, omega) and the free energy (DeltaG(0)) of triple helix formation have been estimated for complexes of oligo(U)(n) (n = 5, 7-10) with poly(A) . poly(U) on the basis of hypochromicity measurements. The data were treated according to the formula of McGhee and von Hippel [J. Mol. Biol. 86 (1974) 469] by a computer program ALAU [H. Schütz et al., Stud. Biophys. 104 (1984) 23] which takes absorbancies and total concentrations as input. In 1 mM cacodylate buffer pH 7.0 with 10 mM NaCl and 10 mM MgCl(2) at 5 degrees C the free energy of contiguous binding was found to be a linear function of the oligomer length with a slope of DeltaG(c,U)(0) = -0.72 (+/-0.03) kcal x mol(-1) per nucleotide. The mean cooperativity coefficient (omega) was 24.5 (+/- 5.6), and the corresponding free energy of interaction between the neighbouring oligonucleotides in the third strand was DeltaG(0(omega)) = -1.74 (+/-0.13) kcal x mol(-1).

Journal Article↗
PubMed2001

Comparison and evaluation of the synthetic biopolymer poly-L-aspartic acid and the synthetic "plastic" polymer poly-acrylic acid for use in metal ion-exchange systems.

Poly-L-aspartic acid (PLAsp), a biopolymer, and a similar synthetic polymer, poly-acrylic acid (PAA), each consisting of approximately 50 repeating Asp and acrylic acid monomers, respectively, were immobilized onto controlled pore glass (CPG) and evaluated for use as metal ion-exchange materials. Both polymers achieve metal complexation primarily through their repeating carboxylate side groups resulting in a similar binding trend for the metals tested (Ca(2+), Cd(2+), Co(2+), Cu(2+), Mg(2+), Mn(2+), Na(+), Ni(2+), Pb(2+)), with metal binding capacities ranging from <0.1 to 12 micromol metal/g column and <0.1 to 32 micromol metal/g column for PLAsp and PAA respectively. Cu(2+) and Pb(2+) exhibited strong binding to both materials, while the other metals demonstrated only weak or minimal binding. Both columns allowed for quantitative release of bound metals through acid stripping and experienced increased overall metal binding with increasing pH. Both systems also maintained similar structural and chemical stability when continuously exposed to neutral buffered, highly acidic, oxidizing, large molecule rich, and elevated temperature environments. The main differences between the two systems are the material cost and system biodegradability.

Acrylates↗
PubMed2000

Core-shell type polymeric nanoparticles composed of poly(L-lactic acid) and poly(N-isopropylacrylamide).

Poly(L-lactic acid)/poly(N-isopropylacrylamide) (abbreviated as LN) block copolymers were synthesized and the LN nanoparticles were prepared by simple diafiltration method. The thermal transition of the LN nanoparticles was at 32.3 degrees C, the lower critical solution temperature (LCST) of the polymer. The fluorescence spectroscopy data showed that LN was self-assembled in water to form core-shell structure nanoparticles, and the critical association concentration (CAC) value was estimated as 1.3x10(-2) g/l. From the transmission electron microscope observations, the LN nanoparticles were spherically shaped and ranged in size between 30 and 50 nm below the LCST. The hydrated size was measured by photon correlation spectroscopy, and reversible size changes were investigated by the factor of temperature. The release of indomethacin from the LN nanoparticles was thermo-sensitive due to the unique characteristic of poly(N-isopropylacrylamide).

Acrylic Resins↗
PubMed2002

Preparation of poly(methacrylic acid-g-poly(ethylene glycol)) nanospheres from methacrylic monomers for pharmaceutical applications.

Nanospheres of poly(methacrylic acid-grafted-poly(ethylene glycol)) were prepared by solution/precipitation polymerization. As colloidal drug delivery carriers, they present unique properties that render them promising candidates for oral protein delivery. The polymerization was carried out in water and the resulting suspension was freeze-dried. As with many colloidal systems, the freeze-dried suspension showed strong agglomeration after drying. The effects of preparation conditions on the particle size and redispersion were investigated using photon correlation spectroscopy. Furthermore, the ability of different types and concentrations of stabilizers (cryoprotectants and steric stabilizers) in preventing this phenomenon was addressed. Pluronics, block copolymers widely used as nonionic surfactants, were the most effective in stabilizing the particles during the freeze-drying process. Pluronic P123, however, increased significantly the particle size of the nanospheres. On the other hand, lyophilizates obtained in the presence of Pluronic F68 had good redispersion properties and no change in particle size was observed.

Drug Compounding↗
PubMed1999

Clonazepam release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(epsilon-caprolactone) and poly(ethylene glycol) macromer.

Poly(ethylene glycol)(PEG) macromers terminated with acrylate groups and semi-interpenetrating polymer networks (SIPNs) composed of poly(epsilon-caprolactone)(PCL) and PEG macromer were synthesized to obtain a bioerodible hydrogel. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Glass transition temperature (Tg) and melting temperature (Tm) of PEG networks and PCL in the SIPNs were inner-shifted, indicating an interpenetration of PCL and PEG chains. Water content in the SIPNs increased with increasing PEG weight fraction due to the hydrophilicity of PEG. The amount of clonazepam (CNZ) released from the SIPNs increased with higher content in the SIPNs, lower drug loading, lower concentration of PEG macromer during the SIPNs preparation, and higher molecular weight of PEG. In particular, a combination with low PEG content and low CNZ solubility in water led to long-term constant release from these matrices in vitro and in vivo.

Animals↗
PubMed2001

Effect of poly(ethylene glycol) graft polymerization of poly(methyl methacrylate) on cell adhesion. In vitro and in vivo study.

PURPOSE: To investigate the effect of surface modification of poly(methyl methacrylate) (PMMA) by poly(ethylene glycol) (PEG) grafting on cell adhesion. SETTING: Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea. METHODS: The PMMA surface was oxidized with ozone, and PEG acrylate was then graft polymerized. To verify the PEG grafting on the surface, the oxygen content was measured by electron spectroscopy for chemical analysis. The contact angle was measured using the Wilhelmy plate method. The adhesion of keratocytes on modified PMMA was investigated in vitro. Cultured rabbit keratocytes (4 x10(5) cells/mL) were layered on each PMMA disk, cultured in a carbon dioxide incubator for 24 hours, harvested by trypsinization, and counted. A commercially available intraocular lens was modified as described and then inserted in the anterior chamber of a white rabbit. The cell adherence pattern on the modified IOL was examined by scanning electron microscopy. RESULTS: The PEG-grafted PMMA revealed a higher oxygen content and lower dynamic receding contact angles than the untreated PMMA. The mean number of adhered cells was 72.5 +/- 22 x 10(4)/mL for untreated PMMA. After PEG grafting of 1 hour and ozone oxidation of 2 hours, the adherent cell counts significantly decreased to 6.5 +/- 1.7 x 10(4)/mL and 7.6 +/- 1.6 x 10(4)/mL, respectively (P =.002). Scanning electron microscopy showed small round cells sparsely scattered on the modified PMMA in contrast to the untreated PMMA. CONCLUSION: Surface modification of PMMA using PEG grafting reduced cell adhesion. This may decrease the incidence of retroprosthetic membrane formation after keratoprosthesis surgery.

Animals↗
PubMed1999

12 year results of a prospective trial comparing poly(methyl methacrylate) and poly(hydroxyethyl methacrylate) intraocular lenses.

PURPOSE: To compare long-term biocompatibility of single-piece poly(methyl methacrylate) (PMMA) and poly(hydroxyethyl methacrylate) (P-HEMA) intraocular lenses (IOLs). SETTING: District General Hospital, United Kingdom. METHODS: In a prospective trial of 250 eyes that had uncomplicated extracapsular cataract extraction, 2 groups of 125 eyes each were matched for age and sex. One group received single-piece looped PMMA IOLs and the other, single-piece solid-haptic P-HEMA IOLs. In all eyes, the IOLs were implanted in the capsular bag at the time of surgery using the envelope technique. RESULTS: Twelve years after surgery, 75 eyes were available for examination. In the PMMA group (40 eyes), 50% had a visual acuity of 20/20 and 50% had intact capsules, many of them with a degree of fibrosis. In the P-HEMA group (35 eyes), 71% had an acuity of 20/20 and 80% had intact capsules (P = .0085). CONCLUSION: In the long term, biocompatibility was better in the P-HEMA group than in the PMMA group.

Aged↗
PubMed2001

Physicochemical properties and nuclease resistance of antisense-oligodeoxynucleotides entrapped in the core of polyion complex micelles composed of poly(ethylene glycol)-poly(L-lysine) block copolymers.

In this study, the physicochemical properties of polyion complex (PIC) micelles formed from antisense-oligodeoxynucleotides (antisense-ODN) and poly(ethylene glycol)-poly(L-lysine) block copolymers (PEG-PLL) were investigated to utilize them as a novel formulation for antisense-ODN delivery. Angular and concentration dependences of the diffusion coefficient of PIC micelles were evaluated by dynamic light scattering. Results suggested that the formed PIC micelles may have spherical shape with core-shell structure, in which the PIC core formed from antisense-ODN and PLL segment was surrounded by a PEG shell. The average radius of PIC micelles was dependent on the chain length of the PLL segment and was not influenced by the change in the length of ODN molecules at least in the range between 15 and 20 base pairs. Critical association concentration (cac) of PIC micelles was then determined from a profile of light scattering intensity versus concentration (Debye plots). Cac is ca. 0.20 mg/ml, which is low enough to ensure the micelle stability in very diluted condition as is the case with systemic injection into the blood compartment for antisense-ODN therapy. Furthermore, the stability of antisense-ODN against deoxyribonuclease I (DNase I) attack was evaluated using capillary gel electrophoresis, revealing that the complexation of antisense-ODN with PEG-PLL effectively prohibited DNase I attack. These characteristics of the PIC micelle system highlight its promising feature as ODN carrier used in the field of targeting therapy.

Deoxyribonuclease I↗
PubMed2002

In vitro phagocytosis and monocyte-macrophage activation with poly(lactide) and poly(lactide-co-glycolide) microspheres.

Treatment of many intracellular infections in the mononuclear phagocytic system (MPS), requires targeting of antibiotics by a drug delivery system. The objective of this study was to examine whether the particular nature of microspheres, made of end-group capped and uncapped poly(lactide) [PLA] and poly(lactide-co-glycolide) [PLGA 50:50 and PLGA 75:25], affect the uptake into and also the activation of monocyte-macrophages. Placebo and gentamicin sulfate containing microspheres were incubated with J774 murine monocyte-macrophages and fresh human blood monocytes. Phagocytosis became more efficient with increasing polymer hydrophobicity, whereas opsonization of the particles in serum exerted inconsistent effects. Monocyte activation was determined by flow cytometry and measured as oxidative burst. The cellular oxidative burst induced by the particles was higher for end-group uncapped polymers. Opsonization increased significantly the oxidative activity of J774 monocytes, but affected inconsistently that of human blood monocytes. The results demonstrate that PLA and PLGA microspheres loaded with gentamicin sulfate were efficiently phagocytosed in vitro. The end-group uncapped polymer-type microspheres promoted significantly cell activation, which may be of importance for drug delivery and targeting to intracellular infections.

Aminoglycosides↗
PubMed2001

Development and characterization of CyA-loaded poly(lactic acid)-poly(ethylene glycol)PEG micro- and nanoparticles. Comparison with conventional PLA particulate carriers.

Cyclosporin A (CyA) loaded poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) micro- and nanoparticles have been developed using an emulsion-solvent evaporation method. Physico-chemical properties, peptide loading content and in vitro release profiles of these novel CyA carriers were compared with those corresponding to conventional PLA micro- and nanoparticles. Results obtained confirm the previously described disposition of PEG chains on the surface of the PLA-PEG formulations. In addition, they revealed the presence of CyA molecules on the surface of both PLA and PLA-PEG systems. Further determination of the surface chemical composition by electron spectroscopy for chemical analysis (ESCA) allowed us to quantify the amount of CyA in the nanospheres' top layers, this amount being higher for nanoparticles than for microparticles, and higher for the PLA systems than for those based on PLA-PEG. In vitro release experiments revealed that PLA-PEG particles provided a more adequate control of CyA release than conventional PLA micro- and nanoparticles. Physico-chemical characterization of the systems during the release studies showed that the developed PLA and PLA-PEG micro- and nanoparticles were not degraded, which suggest a diffusion-mediated release mechanism. Furthermore, we have hypothesized that the hydrophilic outer shell of PEG provides a stationary layer for the diffusion of CyA.

Cyclosporine↗
PubMed1998

Drug diffusion and binding in ionizable interpenetrating networks from poly(vinyl alcohol) and poly(acrylic acid).

Hydrogels of poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA), and their interpenetrating networks (IPNs) were prepared using glutaraldehyde and ethylene glycol dimethacrylate as crosslinking agents. The hydrogels were characterized by measuring their equilibrium polymer volume fraction, equilibrium swelling ratio, and mesh size. Drug and protein diffusion through these hydrogels were studied. Solutes studied included theophylline, vitamin B12 and myoglobin. The ratio of PVA and PAA in the IPNs was varied to study the effect of ionic polymer content on the polymer/drug interactions and on the drug diffusion rate. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was used to analyze the polymer/drug binding interactions. It was concluded that drug diffusion may be impeded by associated drug binding, especially in IPN hydrogels containing high amounts of PAA.

Acrylic Resins↗
PubMed1998

Covalent coupling of immunoglobulin G to a poly(vinyl)alcohol-poly(acrylic acid) graft polymer as a method for fabricating the interfacial-recognition layer of a surface plasmon resonance immunosensor.

The synthesis of a terminally thiolated poly(vinyl)alcohol (PVA) grafted with Poly (acrylic acid) (PAA) side chains is described. The PVA-PAA graft polymer (PVAg) was end-tethered to silver surfaces via the terminal thiol functionality and the resultant mobile, hydrophilic polymer matrix exploited for the covalent immobilization of large quantities of polyclonal goat (anti-hIgG) antibody (IgG) with low levels of non-specific adsorption. An SPR immunosensor, fabricated with an IgG-PVA-silver interfacial layer proved capable of performing a sensitive label-free assay of human IgG antigen (hIgG) with minimal non-specific binding interference. A detection limit (DL) for hIgG from serum of 0.8 microgram/ml (5 nM) and an assay sensitivity of 0.66 ng hIgG/mm2/nM are reported.

Acrylic Resins↗
PubMed2004

Characterization of poly(L-lysine)-graft-poly(ethylene glycol) assembled monolayers on niobium pentoxide substrates using time-of-flight secondary ion mass spectrometry and multivariate analysis.

Control of protein adsorption onto solid surfaces is a critical area of biomaterials and biosensors research. Application of high performance surface analysis techniques to these problems can improve the rational design and understanding of coatings that control protein adsorption. We have used static time-of-flight secondary ion mass spectrometry (TOF-SIMS) to investigate several poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) adlayers adsorbed electrostatically onto negatively charged niobium pentoxide (Nb(2)O(5)) substrates. By varying the PEG graft ratio (i.e., the number of lysine monomers per grafted PEG chain) and the molecular weights of the PLL and PEG polymers, the amount of protein adsorption can be tailored between 1 and 300 ng/cm(2). Detailed multivariate analysis using principal component analysis (PCA) of the positive and negative ion TOF-SIMS spectra showed changes in the outermost surface of the polymer films that were related to the density and molecular weight of the PEG chains on the surface. However, no significant differences were noted due to PLL molecular weight, despite observed differences in the serum adsorption characteristics for adlayers of PLL-g-PEG polymers with different PLL molecular weights. From the PCA results, multivariate peak intensity ratios were developed that correlated with the thickness of the adlayer and the enrichment of the PEG chains and the methoxy terminus of the PEG chains at the outermost surface of the adlayer. Furthermore, partial least squares regression was used to correlate the TOF-SIMS spectra with the amount of protein adsorption, resulting in a predictive model for determining the amount of protein adsorption on the basis of the TOF-SIMS spectra. The accuracy of the prediction of the amount of serum adsorption depended on the molecular weight of the PLL and PEG polymers and the PEG graft ratio. The combination of multivariate analysis and static TOF-SIMS provides detailed information on the surface chemistry and insight into the mechanism for protein resistance of the coatings.

Adsorption↗
PubMed2004

Potentiometric response characteristics of polycation-sensitive membrane electrodes toward poly(amidoamine) and poly(propylenimine) dendrimers.

The potentiometric response characteristics of polycation-sensitive membrane electrodes toward two classes of polycationic dendrimers are examined. Using appropriately formulated polymer membrane electrodes composed of a dinonylnaphthalenesulfonate (DNNS) salt in a plasticized polyurethane matrix, it is shown that poly(amidoamine) (PAMAM) and poly(propylenimine) (PPI) dendrimers are readily detected at submicrogram per milliliter levels via a nonequilibrium response mechanism. The relationship between the total EMF response (at equilibrium) and the specific dendrimer structure is also examined. For both the PAMAM and PPI species, it is shown that the total EMF response does not change significantly with dendrimer generation number; however, the nonequilibrium analytically useful response curves are shifted to higher mass concentrations as the generation number is increased. The relative contributions of the terminal primary amines and the interior tertiary amines of the dendrimers to the observed EMF response are investigated by synthesis of various dendrimer derivatives (acetylated, quaternized, etc.). By comparing the total EMF responses for these derivatives as a function of sample pH, it is demonstrated that the lipophilic cation exchanger (DNNS) within the membrane phase can likely interact electrostatically with both protonated forms of the terminal primary amines and interior tertiary amines of the dendrimer structures. The practical application of the nonequilibrium potentiometric detection of dendrimers for monitoring their interaction with DNA is also demonstrated.

Amines↗