Reduced Skin Photosensitivity with meta-Tetra(hydroxyphenyl)chlorin-Loaded Micelles Based on a Poly(2-ethyl-2-oxazoline)-b-poly(d,l-lactide) Diblock Copolymer in Vivo

2010 ◽  
Vol 7 (4) ◽  
pp. 1244-1253 ◽  
Author(s):  
Ming-Jium Shieh ◽  
Cheng-Liang Peng ◽  
Wei-Lun Chiang ◽  
Chau-Hui Wang ◽  
Chia-Yen Hsu ◽  
...  
Keyword(s):  
Diblock Copolymer ◽  
Skin Photosensitivity

Directing Stem Cell Fate in 3D Through Cell Inert and Adhesive Diblock Copolymer Domains

2013 ◽  
Author(s):  
Somyot Chirasatitsin ◽  
Priyalakshmi Viswanathan ◽  
Giuseppe Battaglia ◽  
Adam J. Engler
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Adhesion ◽  
Cell Fate ◽  
Diblock Copolymer ◽  
Stem Cell Differentiation ◽  
Stem Cell Fate ◽  
Cell Behaviors ◽  
Cell Structures

Adhesions are important cell structures required to transduce a variety of chemical and mechanics signals from outside-in and vice versa, all of which regulate cell behaviors, including stem cell differentiation (1). Though most biomaterials are coated with an adhesive ligand to promote adhesion, they do not often have a uniform distribution that does not match the heterogeneously adhesive extracellular matrix (ECM) in vivo (2). We have previously shown that diblock copolymer (DBC) mixtures undergo interface-confined de-mixing to form nanodomins of one copolymer in another (3). Here we demonstrate how diblock copolymer mixtures can be made into foams with nanodomains to better recapitulate native ECM adhesion regions and influence cell adhesion.

In Vitro and in Vivo Release of Albumin Using a Biodegradable MPEG-PCL Diblock Copolymer as an in Situ Gel-Forming Carrier

2007 ◽  
Vol 8 (4) ◽  
pp. 1093-1100 ◽  
Author(s):  
Hoon Hyun ◽  
Yu Han Kim ◽  
In Bum Song ◽  
Jung Won Lee ◽  
Moon Suk Kim ◽  
...  
Keyword(s):  
Diblock Copolymer ◽  
In Situ Gel ◽  
In Vivo Release

In vivo efficacy of an intratumorally injected in situ-forming doxorubicin/poly(ethylene glycol)-b-polycaprolactone diblock copolymer

Biomaterials ◽  
2011 ◽  
Vol 32 (20) ◽  
pp. 4556-4564 ◽  
Author(s):  
Yun Mi Kang ◽  
Gyeong Hae Kim ◽  
Jae Il Kim ◽  
Da Yeon Kim ◽  
Bit Na Lee ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Diblock Copolymer ◽  
Poly Ethylene Glycol ◽  
In Vivo Efficacy ◽  
In Situ Forming ◽  
Poly Ethylene

Composition of α-tocopheryl acetate with micellar nanocarriers and the possibility of its use as a biologically active additive

2020 ◽  
Vol 42 (4) ◽  
pp. 292-306
Author(s):  
N.M. Permyakova ◽  
◽  
T.B. Zheltonozhskaya ◽  
V.I. Karpovskyi ◽  
R.V. Postoi ◽  
...  
Keyword(s):  
Diblock Copolymer ◽  
Biological Action ◽  
Ethanol Solution ◽  
Biologically Active ◽  
Tocopheryl Acetate ◽  
Similar Process ◽  
Salting Out ◽  
The Stability ◽  
Over Time

Based on the asymmetric diblock copolymer (DBC) poly(ethylene oxide)/polyacrylic acid, effective, biocompatible and biodegradable micellar carriers were obtained for the delivery of vitamin E analogue, α-tocopheryl acetate (α-TOCA), in living organisms. The monitoring of the stability of micellar structures of the block copolymer and its composition with α-TOCA over time, in a saline solution and when the pH of the solution changes, was carried out. The stability of DBC micelles over time at pH = 3.5, partial disaggregation of micelles at pH = 9 and an increase in their aggregation in physiological solution were shown. The high stability of the α-TOCA/DBC composition formed in situ in time in the range of pH=3.5-9 and a significant decrease in its solutions of salting out effects in the presence of NaCl were established. The thermodynamic parameters of the process of the micelle formation of the pure α-TOCA in water/ethanol solution (95/5 v/v) as well as the size and morphology of its micellar structures were determined by light scattering and TEM methods. The initial α-TOCA micelles in water/ethanol solution were stable over a wide pH range, but their stability was much lower and the sensitivity to the presence of NaCl was much higher than that of DBC micelles. The dialysis method revealed the gradual release of the drug from the micellar carrier through a semipermeable membrane into the surrounding aqueous and aqueous-saline media. However, the rate and efficiency of α-TOCA release from the DBC micelles in an aqueous medium were significantly lower compared to a similar process of drug release from the pure α-TOCA dispersion. Thus, a possibility of providing of long-term controlled release of α-TOCA in the living organism due to the use of DBC micelles has been proven. Based on in vivo tests of the biological action of the composition on pregnant sows, its high bioavailability, rapid absorption, active participation in metabolic processes and positive effect on the reproductive qualities of sows compared to pure α-TOCA, were displayed, which improves the safety and productivity of newborn piglets. Key words: diblock copolymer, α-tocopheryl acetate, micellar carrier, encapsulation/release, biological action.

scholarly journals The Use of Radioactive Marker as a Tool to Evaluate the Drug Release in Plasma and Particle Biodistribution of Block Copolymer Nanoparticles

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Sharon Johnstone ◽  
Steven Ansell ◽  
Sherwin Xie ◽  
Lawrence Mayer ◽  
Paul Tardi
Keyword(s):  
Block Copolymer ◽  
Drug Release ◽  
Diblock Copolymer ◽  
Plasma Clearance ◽  
Nanoparticle Stability ◽  
Nanoparticle Formulation ◽  
Formulation Variables

Diblock copolymer nanoparticles encapsulating a paclitaxel prodrug, Propac 7, have been used to demonstrate the usefulness of a nonmetabolizable radioactive marker, cholesteryl hexadecyl ether (CHE), to evaluate nanoparticle formulation variables. Since CHE did not exchange out of the nanoparticles, the rate of clearance of the CHE could be used as an indicator of nanoparticle stability in vivo. We simultaneously monitored prodrug circulation and carrier circulation in the plasma and the retention of CHE relative to the retention of prodrug in the plasma was used to distinguish prodrug release from nanoparticle plasma clearance. Nanoparticles labelled with CHE were also used to evaluate accumulation of nanoparticles in the tumour. This marker has provided relevant data which we have applied to optimise our nanoparticle formulations.

scholarly journals Iron chelation rescues hemolytic anemia and skin photosensitivity in congenital erythropoietic porphyria

Blood ◽  
2020 ◽  
Vol 136 (21) ◽  
pp. 2457-2468
Author(s):  
Jean-Marc Blouin ◽  
Cécile Ged ◽  
Magalie Lalanne ◽  
Isabelle Lamrissi-Garcia ◽  
Fanny Morice-Picard ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Therapeutic Potential ◽  
Iron Chelation ◽  
Substrate Reduction Therapy ◽  
Erythroid Cell ◽  
Cellular Models ◽  
Congenital Erythropoietic Porphyria ◽  
Skin Photosensitivity

Abstract Congenital erythropoietic porphyria (CEP) is an inborn error of heme synthesis resulting from uroporphyrinogen III synthase (UROS) deficiency and the accumulation of nonphysiological porphyrin isomer I metabolites. Clinical features are heterogeneous among patients with CEP but usually combine skin photosensitivity and chronic hemolytic anemia, the severity of which is related to porphyrin overload. Therapeutic options include symptomatic strategies only and are unsatisfactory. One promising approach to treating CEP is to reduce the erythroid production of porphyrins through substrate reduction therapy by inhibiting 5-aminolevulinate synthase 2 (ALAS2), the first and rate-limiting enzyme in the heme biosynthetic pathway. We efficiently reduced porphyrin accumulation after RNA interference–mediated downregulation of ALAS2 in human erythroid cellular models of CEP disease. Taking advantage of the physiological iron-dependent posttranscriptional regulation of ALAS2, we evaluated whether iron chelation with deferiprone could decrease ALAS2 expression and subsequent porphyrin production in vitro and in vivo in a CEP murine model. Treatment with deferiprone of UROS-deficient erythroid cell lines and peripheral blood CD34+-derived erythroid cultures from a patient with CEP inhibited iron-dependent protein ALAS2 and iron-responsive element–binding protein 2 expression and reduced porphyrin production. Furthermore, porphyrin accumulation progressively decreased in red blood cells and urine, and skin photosensitivity in CEP mice treated with deferiprone (1 or 3 mg/mL in drinking water) for 26 weeks was reversed. Hemolysis and iron overload improved upon iron chelation with full correction of anemia in CEP mice treated at the highest dose of deferiprone. Our findings highlight, in both mouse and human models, the therapeutic potential of iron restriction to modulate the phenotype in CEP.

scholarly journals Exceptionally Stable Fluorous Emulsions for the Intravenous Delivery of Volatile General Anesthetics

2012 ◽  
Vol 116 (3) ◽  
pp. 580-585 ◽  
Author(s):  
Jun-Pil Jee ◽  
Maria C. Parlato ◽  
Mark G. Perkins ◽  
Sandro Mecozzi ◽  
Robert A. Pearce
Keyword(s):  
Particle Size ◽  
Diblock Copolymer ◽  
Diblock Copolymers ◽  
Emulsion Stability ◽  
Rapid Onset ◽  
General Anesthetics ◽  
Sprague Dawley ◽  
Improved Stability ◽  
Righting Reflex

Background IV delivery of volatile fluorinated anesthetics has a number of potential advantages when compared with the current inhalation method of administration. We reported previously that the IV delivery of sevoflurane can be achieved through an emulsion composed of a linear fluorinated diblock copolymer, a stabilizer, and the anesthetic. However, this original emulsion was subject to particle size growth that would limit its potential clinical utility. We hypothesized that the use of bulkier fluorous groups and smaller polyethylene glycol moieties in the polymer design would result in improved emulsion stability while maintaining anesthetic functionality. Methods The authors prepared emulsions incorporating sevoflurane, perfluorooctyl bromide as a stabilizing agent, and combinations of linear fluorinated diblock copolymer and a novel dibranched fluorinated diblock copolymer. Emulsion stability was assessed using dynamic light scattering. The ability of the emulsions to induce anesthesia was tested in vivo by administering them intravenously to 15 male Sprague-Dawley rats and measuring loss of the forepaw righting reflex. Results 20% (volume/volume) sevoflurane emulsions incorporating mixtures of dibranched and linear diblock copolymers had improved stability, with those containing an excess of the dibranched polymers displaying stability of particle size for more than 1 yr. The ED50s for loss of forepaw-righting reflex were all similar, and ranged between 0.55- 0.60 ml/kg body weight. Conclusions Hemifluorinated dibranched polymers can be used to generate exceptionally stable sevoflurane nanoemulsions, as required of formulations intended for clinical use. IV delivery of the emulsion in rats resulted in induction of anesthesia with rapid onset and smooth and rapid recovery.

Doxorubicin-loaded micelles of amphiphilic diblock copolymer with pendant dendron improve antitumor efficacy: In vitro and in vivo studies

2017 ◽  
Vol 534 (1-2) ◽  
pp. 136-143 ◽  
Author(s):  
Siew Hui Voon ◽  
Chin Siang Kue ◽  
Toyoko Imae ◽  
Wen Shang Saw ◽  
Hong Boon Lee ◽  
...  
Keyword(s):  
Diblock Copolymer ◽  
Antitumor Efficacy ◽  
In Vivo Studies ◽  
Amphiphilic Diblock Copolymer

In Vivo Osteogenic Differentiation of Rat Bone Marrow Stromal Cells in Thermosensitive MPEG–PCL Diblock Copolymer Gels

2006 ◽  
Vol 12 (10) ◽  
pp. 2863-2873 ◽  
Author(s):  
M.S. Kim ◽  
Sun Kyung Kim ◽  
Soon Hee Kim ◽  
Hoon Hyun ◽  
Gilson Khang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Diblock Copolymer ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Copolymer Gels ◽  
Rat Bone

Fine Structural Changes in the Microvasculature of the Mouse Pinna: Aging and Radiation Injury

1974 ◽  
Vol 32 ◽  
pp. 54-55
Author(s):  
S. Phyllis Steamer ◽  
Rosemarie L. Devine
Keyword(s):  
Structural Changes ◽  
Radiation Treatment ◽  
Arterial Stenosis ◽  
Ultrastructural Changes ◽  
Vascular Effects ◽  
Microvascular Changes ◽  
Surrounding Connective Tissue ◽  
Fission Neutrons ◽  
Total Body

The importance of radiation damage to the skin and its vasculature was recognized by the early radiologists. In more recent studies, vascular effects were shown to involve the endothelium as well as the surrounding connective tissue. Microvascular changes in the mouse pinna were studied in vivo and recorded photographically over a period of 12-18 months. Radiation treatment at 110 days of age was total body exposure to either 240 rad fission neutrons or 855 rad 60Co gamma rays. After in vivo observations in control and irradiated mice, animals were sacrificed for examination of changes in vascular fine structure. Vessels were selected from regions of specific interest that had been identified on photomicrographs. Prominent ultrastructural changes can be attributed to aging as well as to radiation treatment. Of principal concern were determinations of ultrastructural changes associated with venous dilatations, segmental arterial stenosis and tortuosities of both veins and arteries, effects that had been identified on the basis of light microscopic observations. Tortuosities and irregularly dilated vein segments were related to both aging and radiation changes but arterial stenosis was observed only in irradiated animals.

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