scholarly journals Calcium-independent, pH-regulated effects of S-100 proteins on assembly-disassembly of brain microtubule protein in vitro.

1988 ◽  
Vol 263 (1) ◽  
pp. 106-110
Author(s):  
R Donato
Keyword(s):  
Microtubule Protein ◽  
S 100

scholarly journals Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: Formulation, optimization and in vitro evaluation / Alginatne mikrosfere naproksen natrija obložene Eudragitom S-100: Priprava, optimizacija i in vitro vrednovanje

2012 ◽  
Vol 62 (4) ◽  
pp. 529-545 ◽  
Author(s):  
Anuj Chawla ◽  
Pooja Sharma ◽  
Pravin Pawar
Keyword(s):  
Drug Release ◽  
Sodium Alginate ◽  
Naproxen Sodium ◽  
Drug Loading ◽  
Size Analysis ◽  
Scanning Calorimetry ◽  
Sem Images ◽  
S 100 ◽  
Eudragit S 100

The aim of the study was to prepare site specific drug delivery of naproxen sodium using sodium alginate and Eudragit S-100 as a mucoadhesive and pH-sensitive polymer, respectively. Core microspheres of alginate were prepared by a modified emulsification method followed by cross-linking with CaCl2, which was further coated with the pH dependent polymer Eudragit S-100 (2.5 or 5 %) to prevent drug release in the upper gastrointestinal environment. Microspheres were characterized by FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and evaluated by scanning electron microscopy, particle size analysis, drug loading efficiency, in vitro mucoadhesive time study and in vitro drug release study in different simulated gastric fluids. Stability studies of the optimized formulation were carried out for 6 months. SEM images revealed that the surface morphology was rough and smooth for core and coated microspheres, respectively. Core microspheres showed better mucoadhesion compared to coated microspheres when applied to the mucosal surface of freshly excised goat colon. The optimized batch of core microspheres and coated microspheres exhibited 98.42 ± 0.96 and 95.58 ± 0.74 % drug release, respectively. Drug release from all sodium alginate microsphere formulations followed Higuchi kinetics. Moreover, drug release from Eudragit S-100 coated microspheres followed the Korsmeyer-Peppas equation with a Fickian kinetics mechanism. Stability study suggested that the degradation rate constant of microspheres was minimal, indicating 2 years shelf life of the formulation.

scholarly journals A complex control region of the mouse rRNA gene directs accurate initiation by RNA polymerase I.

1985 ◽  
Vol 5 (3) ◽  
pp. 554-562 ◽  
Author(s):  
K G Miller ◽  
J Tower ◽  
B Sollner-Webb
Keyword(s):  
Initiation Site ◽  
Rrna Gene ◽  
Sufficient Information ◽  
Reaction Conditions ◽  
Cell Extracts ◽  
S 100 ◽  
Initiation Reaction ◽  
Polymerase I

To determine the size and location of the mouse rDNA promoter, we constructed systematic series of deletion mutants approaching the initiation site from the 5' and 3' directions. These templates were transcribed in vitro under various conditions with S-100 and whole-cell extracts. Surprisingly, the size of the rDNA region that determines the level of transcription differed markedly, depending on the reaction conditions. In both kinds of cell extracts, the apparent 5' border of the promoter was at residue ca. -27 under optimal transcription conditions, but as reaction conditions became less favorable, the 5' border moved progressively out to residues -35, -39, and -45. The complete promoter, however, extends considerably further, for under other nonoptimal conditions, we observed major effects of promoter domains extending in the 5' direction to positions ca. -100 and -140. In contrast, the apparent 3' border of the mouse rDNA promoter was at residue ca. +9 under all conditions examined. We also show that the subcloned rDNA region from -39 to +9 contains sufficient information to initiate accurately and that the region between +2 and +9 can influence the specificity of initiation. These data indicate that, although the polymerase I transcription factors recognize and accurately initiate with only the sequences downstream of residue -40, sequences extending out to residue -140 greatly favor the initiation reaction; presumably, this entire region is involved in rRNA transcription in vivo.

scholarly journals Identity and Origin of the ATPase activity associated with neuronal microtubules. I. The ATPase activity is associated with membrane vesicles.

1983 ◽  
Vol 96 (5) ◽  
pp. 1298-1305 ◽  
Author(s):  
D B Murphy ◽  
R R Hiebsch ◽  
K T Wallis
Keyword(s):  
Molecular Weight ◽  
Atpase Activity ◽  
High Molecular Weight ◽  
Brain Tissue ◽  
Membrane Vesicles ◽  
Microtubule Associated Proteins ◽  
In Vitro Assembly ◽  
Microtubule Protein ◽  
Associated Proteins

Microtubule protein purified from brain tissue by cycles of in vitro assembly-disassembly contains ATPase activity that has been postulated to be associated with microtubule-associated proteins (MAPs) and therefore significant for studies of microtubule-dependent motility. In this paper we demonstrate that greater than 90% of the ATPase activity is particulate in nature and may be derived from contaminating membrane vesicles. We also show that the MAPs (MAP-1, MAP-2, and tau factors) and other high molecular weight polypeptides do not contain significant amounts of ATPase activity. These findings do not support the concept of "brain dynein" or of MAPs with ATPase activity.

Formulation and Evaluation of Mucoadhesive Floating Microspheres of Repaglinide

2021 ◽  
pp. 5673-5679
Author(s):  
S. Sivaprasad ◽  
V. Alagarsamy ◽  
M. Prathibha Bharathi ◽  
P.V. Murali Krishna ◽  
K. Sandeeep Kanna
Keyword(s):  
Controlled Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Extended Period ◽  
Entrapment Efficiency ◽  
Sustain Release ◽  
S 100 ◽  
Eudragit S 100 ◽  
Good Flow

The main objective of the present study was to design a controlled release dosage form for an oral anti diabetic drug i.e. repaglinide employing polymers like eudragit s- 100. One of the other objective of this present study was to increase the biological half-life the drug by formulating into microspheres. The microspheres of repaglinide were prepared by solvent evaporation method by using eudragit s-100 and ethyl cellulose as polymers with different concentrations. Formulations (F1-F10) were prepared and evaluated for various micrometric properties and it was observed that though all the formulations were exhibited good flow properties, The F5 formulation exhibits higher in- vitro buoyancy time and entrapment efficiency which is considered for in- vitro and mucoadhesive studies. The FTIR results reveal that there was no interaction between the drug and the excipients. The in- vitro release profiles of F1-F5 indicated that all formulations showed controlled release over an extended period, with acceptable release kinetics. Among the all formulations F5 were considered as a promising candidate for sustain release of repaglinide.

scholarly journals Preclinical Pharmacokinetics of C118P, a Novel Prodrug of Microtubules Inhibitor and Its Metabolite C118 in Mice, Rats, and Dogs

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2883 ◽  
Author(s):  
Cang Zhang ◽  
Xiaolan Zhang ◽  
Guangji Wang ◽  
Ying Peng ◽  
Xueyuan Zhang ◽  
...  
Keyword(s):  
Clinical Development ◽  
High Dose ◽  
Protein Inhibitor ◽  
Promising Candidate ◽  
Preclinical Pharmacokinetics ◽  
Tumor Bearing ◽  
Microtubule Protein ◽  
Further Development

C118P, a phosphate prodrug of C118, which is a novel microtubule protein inhibitor, is currently under Phase I clinical development in China for treating ovarian cancer and lung cancer. The preclinical pharmacokinetics of prodrug C118P and its metabolite C118 were extensively characterized in vivo in mice, rats, and dogs and in vitro to support the further development of C118P. The preclinical tissue distribution and excretion were investigated in rats. Plasma protein binding in mice, rat, and human, and hepatic microsomal metabolic stability in mice, rat, dog, monkey, and human, were also evaluated. The (AUC0-inf) and C30s of C118P at 50 mg/kg in rats and 6 mg/kg in dogs, and the C2min of C118 at 6 mg/kg in dogs increased less than the dosage increase, suggested nonlinear pharmacokinetic occurred at high dose. As a prodrug, C118P can be quickly hydrolyzed into C118 after an intravenous administration. The unbound C118 in plasma is slightly higher than C118P. C118P can hardly penetrate the tissue, while C118 can distribute widely into tissues. In tumor-bearing nude mice, the concentration of C118 is high in lung, ovary, and tumor, with an extended half-life in tumor. C118P is a promising candidate prodrug for further clinical development.

scholarly journals The assembly of microtubule protein in vitro. The kinetic role in microtubule elongation of oligomeric fragments containing microtubule-associated proteins

1985 ◽  
Vol 227 (2) ◽  
pp. 439-455 ◽  
Author(s):  
P M Bayley ◽  
F M M Butler ◽  
D C Clark ◽  
E J Manser ◽  
S R Martin
Keyword(s):  
Self Assembly ◽  
Protein Concentration ◽  
Wavelength Dependence ◽  
Electrophoretic Analysis ◽  
Slow Phase ◽  
Condensation Polymerization ◽  
Fast Phase ◽  
Microtubule Protein ◽  
Kinetics Of

The kinetics of assembly were studied for bovine and pig microtubule protein in vitro over a range of conditions of pH, temperature, nucleotide and protein concentration. The kinetics are in general biphasic with two major processes of similar amplitude but separated in rate by one order of magnitude. Rates and amplitudes are complex functions of solution conditions. The rates of the fast phase and the slow phase attain limiting values as a function of increasing protein concentration, and are more stringently limited at pH 6.5 than pH 6.95. Such behaviour indicates that mechanisms other than the condensation polymerization of tubulin dimer become rate-limiting at higher protein concentration. The constancy of the wavelength-dependence of light-scattering and ultrastructural criteria indicate that microtubules of normal morphology are formed in both phases of the assembly process. Electrophoretic analysis of assembling microtubule protein shows that MAP- (microtubule-associated-protein-)rich microtubules are formed during the fast phase. The rate of dissociation of oligomeric species on dilution of microtubule protein closely parallels the fast-phase rate in magnitude and temperature-dependence. We propose that the rate of this process constitutes an upper limit to the rate of the fast phase of assembly. The kinetics of redistribution of MAPs from MAP-rich microtubules may be a factor limiting the slow-phase rate. A working model is derived for the self-assembly of microtubule protein incorporating the dissociation and redistribution mechanisms that impose upper limits to the rates of assembly attainable by bimolecular addition reactions. Key roles are assigned to MAP-containing fragments in both phases of microtubule elongation. Variations in kinetic behaviour with solution conditions are inferred to derive from the nature and properties of fragments formed from oligomeric species after the rapid temperature jump. The model accounts for the limiting rate behaviour and indicates experimental criteria to be applied in evaluating the relative contributions of alternative pathways.

scholarly journals Head-to-tail polymerization of microtubules in vitro. Electron microscope analysis of seeded assembly.

1980 ◽  
Vol 84 (1) ◽  
pp. 141-150 ◽  
Author(s):  
L G Bergen ◽  
G G Borisy
Keyword(s):  
Electron Microscope ◽  
Rate Constants ◽  
Dissociation Constants ◽  
Dissociation Rate ◽  
Association Constants ◽  
Directional Growth ◽  
Microtubule Protein ◽  
Electron Microscope Analysis ◽  
Dissociation Rate Constants

Microtubules are polar structures, and this polarity is reflected in their biased directional growth. Following a convention established previously (G. G. Borisy, 1978, J. Mol. Biol. 124:565--570), we define the plus (+) and minus (-) ends of a microtubule as those equivalent in structural orientation to the distal and proximal ends, respectively, of the A subfiber of flagellar outer doublets. Rates of elongation were obtained for both ends using flagellar axonemes as seeds and porcine brain microtubule protein as subunits. Since the two ends of a flagellar seed are distinguishable morphologically, elongation of each end may be analyzed separately. By plotting rates of elongation at various concentrations of subunit protein, we have determined the association and dissociation rate constants for the plus and minus ends. Under our conditions at 30 degrees C, the association constants were 7.2 X 10(6) M-1 s-1 and 2.25 X 10(6) M-1 s-1 for the plus and minus ends, respectively, and the dissociation constants were 17 s-1 and 7 s-1. From these values and Wegner's equations (1976, J. Mol. Biol. 108:139--150), we identified the plus end of the microtubule as its head and calculated "s," the head-to-tail polymerization parameter. Surprisingly small values (s = 0.07 +/- 0.02) were found. The validity of models of mitosis based upon head-to-tail polymerization (Margolis et al., 1978, Nature (Lond.) 272:450--452) are discussed in light of a small value for s.

scholarly journals FORMULATION AND CHARACTERIZATION OF GASTRORETENTIVE FLOATING MICROBALLOONS OF POORLY WATER-SOLUBLE DRUG DIACEREIN

2021 ◽  
Vol 15 (5) ◽  
pp. 8-12
Author(s):  
Kajal Tomer ◽  
Dilip Kumar Gupta
Keyword(s):  
Particle Size ◽  
Entrapment Efficiency ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Diffusion Method ◽  
Acrylic Polymer ◽  
Water Soluble Drug ◽  
Technological Advances ◽  
S 100

The drug can be released in a controlled manner using a gastro retentive dosage type. The main focus on the novel technological advances in the floating drug delivery method for gastric retention. The preparation of diacerein micro balloon is done by solvent diffusion method, using acrylic polymer like Eudragit S 100 and HPMC K4 M. The various evaluation of the prepared floating microsphere like its % yield, drug entrapment efficiency, particle size in-vitro dissolution, buoyancy, was studied. The floating microsphere was found to be spherical and range from 85 μm - 192 μm. Whereas the buoyancy in gastric mucosa between the range 30.5% -49.5%. The % yield and % entrapment efficiency were found under the range 61% - 82% and 45.1–84.1% respectively. The microsphere showed favorable in-vitro dissolution 76.8 to 94.45. The optimized formulation was found based on evaluation of floating micro-balloons, Formulation (M3E3) showed the best result as particle size 192 μm, DDE 84.1%, in vitro drug release 94.5%, and in vitro buoyancy 49.5%. all the formulations showed controlled release up to 24 hours.

scholarly journals Prednisolone Loaded Tamarind Gum Microspheres for Colonic Delivery

2021 ◽  
pp. 324-332
Author(s):  
Harish K. Kunjwani ◽  
Dinesh M. Sakarkar
Keyword(s):  
Drug Release ◽  
Controlled Drug Release ◽  
Local Concentration ◽  
Colonic Delivery ◽  
Simulated Environment ◽  
S 100 ◽  
Long Time ◽  
Sensitive Property ◽  
Microsphere Preparation

The aim of this work was to formulate a novel multiparticulate system having pH sensitive property and specific enzyme biodegradability for colon specific drug delivery of Prednisolone (PD). Natural polysaccharide, Tamarind gum is used for microsphere preparation and Eudratit S- 100 for coating to provide pH controlled drug release. The formulation aims at minimal degradation and optimum delivery of the drug with relatively higher local concentration, which may provide more effective therapy for inflammatory bowel disease including Crohn disease and ulcerative colitis. Tamarind gum microspheres were prepared by emulsion dehydration technique using polymer in ratio of 1:1 to 1: 9. These microspheres were coated with Eudragit S-100 by oil in oil solvent evaporation method using core: coat ration (5:1). Tamarind gum microspheres and Eudragit coated tamarind gum microspheres were evaluated for surface morphology, particle size and size distribution, percentage drug entrapment, surface accumulation studies, in vitro drug release in simulated gastrointestinal fluids. The effect of various formulation variables were studied the prepared microspheres were spherical in shape in the size range of 64 µm to 113 µm, the encapsulation efficiency was in range of 30-72% depending upon the concentration of gum. The drug release was about 14-20% in first four hours of study gradually rises in 5th hour and 85% drug release occurs in 10-12% hr thus showing desirable drug release in the colonic simulated environment. PD tamarind gum microspheres are thought to have the potential to maintain drug concentration within target ranges for a long time, decreasing the side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency. The animal study done using acetic acid induced colitis model on rats also suggest the anti inflammatory activity of the formulation.

Sign in / Sign up

Export Citation Format

Share Document