Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Temperature-sensitive drug release was examined using liposomes mixed with a copolymer of N-isopropylacrylamide (NIPAM) and acrylic acid [P(NIPAM-AA)] i.e., thermally responsive liposomes. P(NIPAM-AA) copolymers with transition temperatures of about 30, 33, 37, and 43 degrees C were synthesized by copolymerizing NIPAM and acrylic acid. Thermally responsive liposomes were prepared by mixing hydrophobically modified PNIPAM, or P(NIPAM-AA) with various liposomes, composed of egg phosphatidylcholine (PC), dimyristoylphosphatidylcholine (DMPC)/dipalmitoylphosphatidylcholine (DPPC) mixture (5: 5, w/w), DPPC, or distearoylphosphatidylcholine (DSPC). The release of a fluorescent marker, calcein, from liposomes was monitored by injecting the liposomal suspension at 17 degrees C into phosphate-buffered saline (PBS, pH 7.4) preadjusted to a temperature ranging from 20 to 46 degrees C. For liposomes of egg PC and DSPC, which do not undergo a phase transition during the temperature jump (17-->20-46 degrees C), the release temperature of the liposomes increased as the content of acrylic acid in the copolymers increased. The interaction between copolymer and lipid may induce the release of calcein at LCST of the copolymer. For DPPC liposomes, the release patterns were similar to those of egg PC and DSPC liposomes at 20-36 degrees C, where the phase transition of the liposomal membrane did not occur, while at 36-46 degrees C, where the phase transition of liposomal membrane occurred, the degree of release was almost the same. For DMPC/DPPC (5:5, w/w) liposomes, where the transition occurred below those of PNIPAMs, equally enhanced releases were observed as compared with PNIPAMs, even below the LCSTs of PNIPAMs. Thus, regardless of the occurrence of the transition of PNIPAMs, phase transition of DMPC/DPPC liposomes controlled the release of calcein.
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PMID:Temperature-sensitivity of liposomal lipid bilayers mixed with poly(N-isopropylacrylamide-co-acrylic acid). 905 85

A series of nanospheres composed of temperature-sensitive poly(N-isopropylacrylamide), poly(ethylene glycol) 400 dimethacrylate, and poly(ethylene glycol) 1000 methacrylate was prepared by a thermally-initiated free radical dispersion polymerization method. Insulin was loaded into the nanoparticles by equilibrium partitioning. The loading capacity of insulin into the nanoparticles was 2.1% (2.1 mg insulin/100 mg nanoparticles). The stability of the loaded insulin at elevated temperatures was investigated by reverse phase high pressure liquid chromatography. The nanoparticles were able to protect the loaded insulin, as more than 80% of the loaded insulin could still be detected compared to 0% for the control (0.1% insulin solution in PBS) when heated to 80 degrees C for 5 h. The stability of the loaded insulin at high shear stress (289 1/s) was also investigated. No significant loss of insulin was detected both from nanoparticles loaded with insulin sample and the control (0.1% insulin solution in PBS). The results showed that shear stress alone did not have a major effect on insulin denaturation. The ability of the nanoparticles to protect the insulin from high temperature and high shear stress made the system a good candidate as a carrier for insulin for fluidized bed coating technology.
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PMID:Preparation of stable insulin-loaded nanospheres of poly(ethylene glycol) macromers and N-isopropyl acrylamide. 1194 11

A hybrid temperature-responsive hydroxyapatite-poly(N-isopropylacrylamide) (HAP-PNIPAAm) gel has been synthesized by the interpenetration of PNIPAAm into a sintered HAP disk through a radical-initiated polymerization of NIPAAm monomers under N2 atmosphere, and shows sustained positive thermo-responsive drug release profile over a month at PBS buffer.
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PMID:Sustained drug release on temperature-responsive poly(N-isopropylacrylamide)-integrated hydroxyapatite. 1219 65

A series of graft copolymers consisting of either poly(N-isopropylacrylamide) (PNiPAAm) or poly(N,N-diethylacrylamide) (PDEAAm) as a thermo-responsive component in the polymer backbone and poly(ethyleneglycol) (PEG) were immobilized as thin films and cross-linked on a fluoropolymer substrate using low-pressure argon plasma treatment. The surface-immobilized hydrogels exhibit a transition from partially collapsed to completely swollen, which is in the range of 32-35 degrees C and corresponds to the lower critical solution temperature of the soluble polymers. The hydrogels were used as cell carriers in culture experiments with L929 mouse fibroblast cells to probe for cell adhesion, proliferation, and temperature-dependent detachment of cell layers. The fibroblast cells adhere, spread, and proliferate on the hydrogel layers at 37 degrees C and become completely detached after reducing the temperature by 3 K. The cell release characteristics were further correlated to the swelling and collapsing behavior of the hydrogel films and the polymer solutions as measured in PBS solution and RPMI cell cultivation medium. It could be shown that, long before the swelling has completed upon temperature reduction, the cells detach. This can be attributed to the large content of PEG present in the hydrogel, which weaken the cell adhesion strength to the hydrogel layers.
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PMID:Thermo-responsive PNiPAAm-g-PEG films for controlled cell detachment. 1460 3

Temperature-sensitive diblock copolymers, poly(N-isopropylacrylamide)-b-poly(D,L-lactide) (PNIPAAm-b-PLA) with different PNIPAAm contents were synthesized and utilized to fabricate microspheres containing bovine serum albumin (BSA, as a model protein) by a water-in-oil-in-water double emulsion solvent evaporation process. XPS analysis showed that PNIPAAm was a dominant component of the microspheres surface. BSA was well entrapped within the microspheres, and more than 90% encapsulation efficiency was achieved. The in vitro degradation behavior of microspheres was investigated using SEM, NMR, FTIR, and GPC. It was found that the microspheres were erodible, and polymer degradation occurred in the PLA block. Degradation of PLA was completed after 5 months incubation in PBS (pH 7.4) at 37 degrees C. A PVA concentration of 0.2% (w/v) in the internal aqueous phase yielded the microspheres with an interconnected porous structure, resulting in fast matrix erosion and sustained BSA release. However, 0.05% PVA produced the microspheres with a multivesicular internal structure wrapped with a dense skin layer, resulting in lower erosion rate and a biphasic release pattern of BSA that was characterized with an initial burst followed by a nonrelease phase. The microspheres made from PNIPAAm-b-PLA with a higher portion of PNIPAAm provided faster BSA release. In addition, BSA release from the microspheres responded to the external temperature changes. BSA release was slower at 37 degrees C (above the LCST) than at a temperature below the LCST. The microspheres fabricated with PNIPAAm-b-PLA having a 1:5 molar ratio of PNIPAAm to PLA and 0.2% (w/v) PVA in the internal aqueous phase provided a sustained release of BSA over 3 weeks in PBS (pH 7.4) at 37 degrees C.
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PMID:Preparation and characterization of temperature-sensitive poly(N-isopropylacrylamide)-b-poly(D,L-lactide) microspheres for protein delivery. 1460 9

The thermally responsive cholesteryl end-capped poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and cholesteryl grafted poly[N-isopropylacrylamide-co-N-(hydroxymethyl) acrylamide] amphiphilic polymers were synthesized and utilized to encapsulate cyclosporin A (CyA) and indomethacin (IND) within core-shell nanoparticles by a membrane dialysis method. The blank and drug-loaded nanoparticles were characterized using various analytical tools. The blank nanoparticles had a mean diameter less than 100 nm, whereas the drug-loaded nanoparticles were between 100 and 200 nm in diameter. The CAC value of cholesteryl end-capped and grafted polymers in PBS (pH 7.4) was estimated to be 16 and 8.5mg/l, respectively. The LCST value for both nanoparticle systems in PBS (pH 7.4) was determined to be 33.4 degrees C and 38.3 degrees C, respectively. The presence of proteins in PBS reduced the LCST. The core-shell nanoparticles provided great capacity for drug loading. In particular, the cholesteryl grafted polymer yielded a higher encapsulation efficiency for drugs. Compared to CyA, better entrapment was observed for IDN. A reduced fabrication temperature provided greater drug encapsulation efficiency. An increase in the initial drug content yielded lower drug encapsulation efficiencies at 10 degrees C and 15 degrees C. Increasing the polymer concentration increased drug encapsulation efficiency. The drug-loading process was analyzed to understand the effect of various fabrication parameters on drug encapsulation efficiency. IND release from the nanoparticles was responsive to temperature changes, being faster at a temperature around the LCST than below the LCST.
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PMID:Thermally responsive core-shell nanoparticles self-assembled from cholesteryl end-capped and grafted polyacrylamides:; drug incorporation and in vitro release. 1504 20

Poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAM-HA) and PNIPAM-grafted gelatin (PNIPAM-gelatin), which exhibit sol-to-gel transformation at physiological temperature, were applied as control of tissue adhesions: tissue adhesion prevention material and hemostatic aid, respectively. The rat cecum, which was abraded using surgical gauze, was coated with PNIPAM-HA-containing PBS (concentration: 0.5 w/v%). The coated solution was immediately converted to an opaque precipitate at body temperature, which weakly adhered to and covered the injured rat cecum. One week after coating, tissue adhesion between the PNIPAM-HA-treated cecum and adjacent tissues was significantly reduced as compared with that between non-treated tissue and adjacent tissues. On the other hand, the coating of bleeding spots of a canine liver with PNIPAM-gelatin-containing PBS (concentration: 20 w/v%) resulted in spontaneous gel formation on the tissues and subsequently suppressed bleeding. Although these thermoresponsive tissue adhesion prevention and hemostatic materials are still prototypes at this time, both thermoresponsive biomacromolecules bioconjugated with PNIPAM, PNIPAM-HA and PNIPAM-gelatin, may serve as a tissue adhesion prevention material and hemostatic aid, respectively.
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PMID:The potential of poly(N-isopropylacrylamide) (PNIPAM)-grafted hyaluronan and PNIPAM-grafted gelatin in the control of post-surgical tissue adhesions. 1528 43

Thermoresponsive and injectable semi-interpenetrating polymer networks (sIPNs) containing a biospecific cell-adhesive signal and proteolytically degradable domains were developed as a synthetic equivalent of the extracellular matrix (ECM). The sIPNs synthesized define a modular hydrogel ECM where different properties of the matrix can be manipulated independently, thus creating a system where parametric analysis of the effect of hydrogel properties on cell proliferation and differentiation is possible. sIPNs composed of poly(N-isopropylacrylamide-co-acrylic acid) [p(NIPAAm-co-AAc)] and RGD-grafted poly(acrylic acid) linear chains [p(AAc)-g-RGD] were synthesized with peptide crosslinkers containing a matrix metalloproteinase-13 (MMP-13, collagenase-3) degradable domain. The lower critical solution temperature (LCST) of peptide-crosslinked p(NIPAAm-co-AAc) sIPNs was not influenced by the addition of either linear p(AAc) or peptide-modified p(AAc) chains ( approximately 34 degrees C) in PBS. Degradation of peptide-crosslinked hydrogels and sIPNs was enzyme specific and concentration dependent. Exposure of rat calvarial osteoblast (RCO) culture to the degradation products from the peptide-crosslinked hydrogels did not significantly affect cell viability. Migration of RCOs into the sIPNs was dependent upon the presence of both a cell-adhesive RGD peptide (Ac-CGGNGEPRGDTYRAY-NH2) and proteolytically-degradable crosslinks; however, there was greater dependence on the latter. The sIPNs synthesized are versatile materials for assessing cell fate in synthetic ECM constructs in vitro and tissue regeneration in vivo.
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PMID:Synthetic MMP-13 degradable ECMs based on poly(N-isopropylacrylamide-co-acrylic acid) semi-interpenetrating polymer networks. I. Degradation and cell migration. 1604 78

Thermally responsive amphiphilic poly(N-isopropylacrylamide) (PNIPAm)-grafted-polyphosphazene (PNIPAm-g-PPP) was synthesized by stepwise cosubstitution of chlorine atoms on polymer backbones with amino-terminated NIPAm oligomers and ethyl glycinate (GlyEt). Polymer structure was confirmed by FT-IR, (1)H NMR, elemental analysis, and GPC. The thermosensitivity of PNIPAm-g-PPP aqueous solution was investigated by turbidity method. The lower critical solution temperature (LCST) of PNIPAm-g-PPP was observed to be approximately 30 degrees C in water, while it was 24 degrees C in 0.1M PBS (pH 7.4). Micellization behavior of PNIPAm-g-PPP in aqueous solution was characterized by fluorescence probe technique, TEM, and DLS. The critical micelle concentration (CMC), thus, determined was 0.0187 g/L. Both TEM and DLS measurement suggested that the diameter of micelles was approximately 190 nm at 20 degrees C. Diflunisal (DIF)-loaded micelles were prepared by dialysis method. In vitro release test at various temperatures was also performed to study the effect of temperature on the drug release profiles. It was demonstrated that DIF release from PNIPAm-g-PPP micelles was slower at the temperature of 37 degrees C than that at 4 degrees C.
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PMID:Thermally responsive polymeric micelles self-assembled by amphiphilic polyphosphazene with poly(N-isopropylacrylamide) and ethyl glycinate as side groups: polymer synthesis, characterization, and in vitro drug release study. 1634 95

The goal of this work is to make an injectable physically and chemically cross-linking NIPAAm-based copolymer system for endovascular embolization. A copolymer with N-isopropylacrylamide (NIPAAm) and hydroxyethyl methacrylate (HEMA) was synthesized and converted to poly(NIPAAm-co-HEMA-acrylate) functionalized with olefins. When poly(NIPAAm-co-HEMA-acrylate) was mixed with pentaerythritol tetrakis 3-mercaptopropionate (QT) stoichiometrically in a 0.1 N PBS solution of pH 7.4, it formed a temperature-sensitive hydrogel with low swelling through the Michael-type addition reaction and showed improved elastic properties at low frequency compared to physical gelation. This material could be useful for applications requiring water-soluble injection but lower swelling and lower creep properties than available with other soluble in-situ-gelling materials.
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PMID:In-situ injectable physically and chemically gelling NIPAAm-based copolymer system for embolization. 1676 34


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