scholarly journals Release of Pharmaceutical Peptides in an Aggregated State: Using Fibrillar Polymorphism to Modulate Release Levels

2019 ◽  
Vol 3 (1) ◽  
pp. 42 ◽  
Author(s):  
Jens Madsen ◽  
Gunna Christiansen ◽  
Lise Giehm ◽  
Daniel Otzen
Keyword(s):  
Control Release ◽  
Proteinase K ◽  
Sustained Delivery ◽  
Soluble Peptide ◽  
Surfactant Aggregates ◽  
Dodecyl Maltoside ◽  
Multiple Cycles ◽  
The Stability ◽  
Traditional Approaches ◽  
Release Profiles

Traditional approaches to achieve sustained delivery of pharmaceutical peptides traditionally use co-excipients (e.g., microspheres and hydrogels). Here, we investigate the release of an amyloidogenic glucagon analogue (3474) from an aggregated state and the influence of surfactants on this process. The formulation of peptide 3474 in dodecyl maltoside (DDM), rhamnolipid (RL), and sophorolipid (SL) led to faster fibrillation. When the aggregates were subjected to multiple cycles of release by repeated resuspension in fresh buffer, the kinetics of the release of soluble peptide 3474 from different surfactant aggregates all followed a simple exponential decay fit, with half-lives of 5–18 min and relatively constant levels of release in each cycle. However, different amounts of peptide are released from different aggregates, ranging from 0.015 mg/mL (3475-buffer) up to 0.03 mg/mL (3474-DDM), with 3474-buffer and 3474-RL in between. In addition to higher release levels, 3474-DDM aggregates showed a different amyloid FTIR structure, compared to 3474-RL and 3474-SL aggregates and a faster rate of degradation by proteinase K. This demonstrates that the stability of organized peptide aggregates can be modulated to achieve differences in release of soluble peptides, thus coupling aggregate polymorphism to differential release profiles. We achieved aggregate polymorphism by the addition of different surfactants, but polymorphism may also be reached through other approaches, including different excipients as well as changes in pH and salinity, providing a versatile handle to control release profiles.

DEVS OS (Discrete Even Visualization and Simulation Operating System)

2018 ◽  
Author(s):  
Adnan Hajar
Keyword(s):  
Operating System ◽  
Operating Systems ◽  
Scheduling Algorithm ◽  
The Novel ◽  
Priority Scheduling ◽  
First Come First Serve ◽  
Multiple Cycles ◽  
Visualization And Simulation ◽  
Traditional Approaches

The use of traditional approaches to teach Operating Systems usually lacks the visual aspect. The following research investigates the novel use of DEVS (Discrete Even Visualization and Simulation) in simulating the operation of an operating system. Cd boost++ was the framework of choice for this project. The simulation successfully mimicked the work of an operating system by simulating multiple cycles of program requests. This simulation is capable of further enhance the explanation of how an operating system works. The cases studied in this work include: 1- two processes running concurrently doing multiple IO’s, 2-four processes running concurrently based on a first come first serve scheduling algorithm, and 3- 20 processes running concurrently using highest priority scheduling algorithm. Output observation of the last case show promising results of successful use of DEVS and cd boost++ as a framework to build an operating system.

Sustainability of antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of moderately (MEC) and highly (HEC) emetogenic chemotherapy regimens: Results of a randomized phase III trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9626-9626
Author(s):  
Ralph V. Boccia ◽  
William Cooper ◽  
Erin O'Boyle
Keyword(s):  
Rescue Medication ◽  
Emetogenic Chemotherapy ◽  
Phase Iii ◽  
Sustained Delivery ◽  
Test Results ◽  
Phase Iii Trial ◽  
Multiple Cycles ◽  
To Receive ◽  
Delayed Phase ◽  
Clinical Trial Information

9626 Background: Patients receiving MEC or HEC were administered subcutaneous (SC) APF530 500 mg, a sustained delivery formulation of granisetron (10 mg). The complete antiemetic response rates (CR; no emetic episodes and no rescue medication) were non-inferior to those of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) (Grous et al. ASCO 2009, #9627). We report on sustainability of CR with APF530 (10 mg) during multiple chemotherapy cycles in this study. Methods: 1428 patients scheduled to receive single doses of MEC or HEC were randomized to APF530 SC (5 or 10 mg granisetron) or 0.25 mg palonosetron intravenously (IV) prior to cycle 1 (C1). In C2-4, patients who received palonosetron in C1 were randomized to APF530 5 or 10 mg; those who received APF530 continued with their C1 APF530 dose. Treatment cycles were separated by 7-28 days. CR rates were compared between cycles using McNemar’s test. Results: No significant differences in within-cycle CR occurred between APF530 doses during acute and delayed phases in C2-4 for MEC and HEC, but a trend toward higher CR rates was seen in successive cycles. For the 2 doses, CR was sustained across all 4 cycles in 56.5-62.6% and 68.4-71.7% in acute phase, and 41.8-42.4% and 57.5-57.9% in delayed phase with MEC and HEC, respectively. Examination of CR rates in C2, C3, or C4 compared with the rate in C1 showed that CR rates were sustained and that the proportion of patients with no CR in C1 but CR in later cycles was consistently higher than that of patients with CR in C1 but no CR later. For illustration, the table shows C4 CR and C1 CR for patients who received APF530 10 mg in C1 and C4. Conclusions: CR rates achieved with APF530 during acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles. Clinical trial information: NCT00343460. [Table: see text]

The stability of pseudopeptides bearing sulfoximines as chiral backbone modifying element towards proteinase K

2003 ◽  
Vol 13 (19) ◽  
pp. 3207-3211 ◽  
Author(s):  
Carsten Bolm ◽  
Dirk Müller ◽  
Christian Dalhoff ◽  
Christian P.R. Hackenberger ◽  
Elmar Weinhold
Keyword(s):  
Proteinase K ◽  
The Stability

scholarly journals A fixative suitable for in situ hybridization histochemistry.

1993 ◽  
Vol 41 (6) ◽  
pp. 947-953 ◽  
Author(s):  
F Uehara ◽  
N Ohba ◽  
Y Nakashima ◽  
T Yanagita ◽  
M Ozawa ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Proteinase K ◽  
Optimal Time ◽  
Hybridization Histochemistry ◽  
Tissue Sections ◽  
In Situ Hybridization Histochemistry ◽  
Rna Probes ◽  
Labeled Rna ◽  
The Stability

We compared the morphology and stability of hybridization signals between paraffin sections of rat retina fixed with commonly used 4% paraformaldehyde/PBS and those fixed with a fixative containing glutaraldehyde in in situ hybridization histochemistry, using a digoxigenin-labeled RNA probe complementary for beta-galactoside alpha 2,6-sialyltransferase mRNA. Retinal detachment was frequently observed in the sections fixed with 4% paraformaldehyde-PBS, whereas the morphology was satisfactorily preserved in those fixed with either 0.5% glutaraldehyde, 4% paraformaldehyde-PBS, or 2.5% glutaraldehyde-PBS. Without glutaraldehyde, it was difficult to determine the most appropriate length of proteinase K digestion of tissue sections for facilitating probe penetration, since the optimal time for definite hybridization was variable among the retinal cells in heterogeneous layers. By addition of glutaraldehyde to paraformaldehyde or with glutaraldehyde alone, it was easy to establish the appropriate time for the unmasking procedure, since intense mRNA signals were constant throughout the retina by proteinase K digestion for more than 30-40 min. Using a fixative that causes stronger cross-linking (e.g., glutaraldehyde) is recommended to improve not only the morphology but also the stability of hybridization signals in in situ hybridization histochemistry with paraffin embedding and digoxigenin-labeled RNA probes.

Bioresorbable polypeptide-based comb-polymers efficiently improves the stability and pharmacokinetics of proteins in vivo

2017 ◽  
Vol 5 (4) ◽  
pp. 837-848 ◽  
Author(s):  
Md. Hasan Turabee ◽  
Thavasyappan Thambi ◽  
Jae Seung Lym ◽  
Doo Sung Lee
Keyword(s):  
Growth Hormone ◽  
Phase Transitions ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Sustained Delivery ◽  
Amphiphilic Copolymers ◽  
Comb Polymers ◽  
Gel Phase ◽  
The Stability

Polypeptide-based comb-like amphiphilic copolymers that exhibits sol-to-gel phase transitions in response to physiological pH and temperature have been developed for the sustained delivery of human growth hormone.

Metal-Ion Depletion Impacts the Stability and Performance of Battery Electrode Deionization over Multiple Cycles

2021 ◽  
Author(s):  
Le Shi ◽  
Evan Newcomer ◽  
Moon Son ◽  
Vineeth Pothanamkandathil ◽  
Christopher A. Gorski ◽  
...  
Keyword(s):  
Metal Ion ◽  
Battery Electrode ◽  
Multiple Cycles ◽  
And Performance ◽  
The Stability ◽  
Ion Depletion

scholarly journals Prebiotically Plausible ‘Patching’ of RNA Backbone Cleavage Through a 3′-5′ Pyrophosphate Linkage

2019 ◽  
Author(s):  
Tom H. Wright ◽  
Constantin Giurgiu ◽  
Aleksandar Radakovic ◽  
Derek K. O’Flaherty ◽  
Lijun Zhou ◽  
...  
Keyword(s):  
Genetic Information ◽  
Prebiotic Chemistry ◽  
Rna World ◽  
Rna Replication ◽  
Cellular Biology ◽  
Backbone Cleavage ◽  
Phosphodiester Backbone ◽  
Rna Backbone ◽  
Multiple Cycles ◽  
The Stability

ABSTRACTAchieving multiple cycles of RNA replication within a model protocell would be a critical step towards demonstrating a path from prebiotic chemistry to cellular biology. Any model for early life based on an ‘RNA world’ must account for RNA strand cleavage and hydrolysis, which would degrade primitive genetic information and lead to an accumulation of truncated, phosphate-terminated strands. We show here that cleavage of the phosphodiester backbone is not an endpoint for RNA replication. Instead, 3′ -phosphate terminated RNA strands are able to participate in template-directed copying reactions with activated ribonucleotide monomers. These reactions form a pyrophosphate linkage, the stability of which we have characterized in the context of RNA copying chemistry. We found that the pyrophosphate bond is relatively stable within an RNA duplex and in the presence of chelated magnesium. Under these conditions, pyrophosphate-RNA can act as a temporary ‘patch’ to template the polymerization of canonical ribonucleotides, suggesting a plausible non-enzymatic pathway for the salvage and recovery of genetic information following strand cleavage.

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