scholarly journals Transdermal Transport In Vitro of Domperidone by Compartmental Modeling Approach

2021 ◽  
Author(s):  
Sekar Ayu Pawestri ◽  
Akhmad Kharis Nugroho ◽  
Endang Lukitaningsih
Keyword(s):  
Transport Mechanism ◽  
Goodness Of Fit ◽  
Transport Model ◽  
Compartmental Models ◽  
Uv Spectrophotometry ◽  
Compartmental Modeling ◽  
Vertical Diffusion ◽  
Receptor Compartment ◽  
Transdermal Transport

Transdermal delivery can be alternatively chosen for domperidone to improve its low oral bioavailability. Development drugs into transdermal formulation need information about the transport mechanism of the drug. The purpose of this study was to develop models of domperidone transdermal transport in vitro based on compartmental modeling for understanding the domperidone transport mechanism. Domperidone solution (0,5 g/L in a citric buffer, pH 5) was filled into the donor compartment. The comparative study also conducted to examine the effect of different pH on domperidone transdermal transport in pH 1 (4g/L in 0,1 M HCl). The shed snake-skin and cellophane membrane were pretreated for 1 hour with chemical enhancers (oleic acid in propylene glycol) and assembled between the donor and the receptor compartment of the vertical diffusion cell. The receptor compartment was filled in with phosphate-buffered saline at a pH of 6.8. The permeation study was performed for 8 hours. Samples concentration was assayed by the UV-Spectrophotometry method. The cumulative permeation profiles of domperidone were analyzed using WinSAAM. Three and four-compartmental models were proposed with the one lag compartment. The evaluation of the appropriate number of compartments in the transport model was examined based on the visual goodness of fit (GOF) and the Corrected Akaike’s Information Criterion (AICc) values. Four-compartmental models with one lag compartment were the best model describing percutaneous domperidone transport either in pH donor of 5 or pH 1. The model indicates domperidone transport follows into two parallel routes, including a lag compartment.

scholarly journals Dexamethasone-Loaded Lipomers: Development, Characterization, and Skin Biodistribution Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 533
Author(s):  
Eloy Pena-Rodríguez ◽  
Maria Lajarin-Reinares ◽  
Aida Mata-Ventosa ◽  
Sandra Pérez-Torras ◽  
Francisco Fernández-Campos
Keyword(s):  
In Vitro Release ◽  
Human Keratinocytes ◽  
Topical Administration ◽  
In Vitro Cytotoxicity ◽  
Hair Follicles ◽  
Vertical Diffusion ◽  
Biodistribution Studies ◽  
Follicular Targeting ◽  
Depot Effect

Follicular targeting has gained more attention in recent decades, due to the possibility of obtaining a depot effect in topical administration and its potential as a tool to treat hair follicle-related diseases. Lipid core ethyl cellulose lipomers were developed and optimized, following which characterization of their physicochemical properties was carried out. Dexamethasone was encapsulated in the lipomers (size, 115 nm; polydispersity, 0.24; zeta-potential (Z-potential), +30 mV) and their in vitro release profiles against dexamethasone in solution were investigated by vertical diffusion Franz cells. The skin biodistribution of the fluorescent-loaded lipomers was observed using confocal microscopy, demonstrating the accumulation of both lipomers and fluorochromes in the hair follicles of pig skin. To confirm this fact, immunofluorescence of the dexamethasone-loaded lipomers was carried out in pig hair follicles. The anti-inflammatory (via TNFα) efficacy of the dexamethasone-loaded lipomers was demonstrated in vitro in an HEK001 human keratinocytes cell culture and the in vitro cytotoxicity of the nanoformulation was investigated.

scholarly journals Insights into the Antioxidant Mechanism of Newly Synthesized Benzoxazinic Nitrones: In Vitro and In Silico Studies with DPPH Model Radical

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1224
Author(s):  
Stefania Marano ◽  
Cristina Minnelli ◽  
Lorenzo Ripani ◽  
Massimo Marcaccio ◽  
Emiliano Laudadio ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Epr Spectroscopy ◽  
Point Of View ◽  
Uv Spectrophotometry ◽  
Design And Synthesis ◽  
Antioxidant Mechanism ◽  
Primary Mechanism ◽  
In Silico Studies ◽  
Wide Range

Synthetic nitrone spin-traps are being explored as therapeutic agents for the treatment of a wide range of oxidative stress-related pathologies, including but not limited to stroke, cancer, cardiovascular, and neurodegenerative diseases. In this context, increasing efforts are currently being made to the design and synthesis of new nitrone-based compounds with enhanced efficacy. The most researched nitrones are surely the ones related to α-phenyl-tert-butylnitrone (PBN) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) derivatives, which have shown to possess potent biological activity in many experimental animal models. However, more recently, nitrones with a benzoxazinic structure (3-aryl-2H-benzo[1,4]oxazin-N-oxides) have been demonstrated to have superior antioxidant activity compared to PBN. In this study, two new benzoxazinic nitrones bearing an electron-withdrawing methoxycarbonyl group on the benzo moiety (in para and meta positions respect to the nitronyl function) were synthesized. Their in vitro antioxidant activity was evaluated by two cellular-based assays (inhibition of AAPH-induced human erythrocyte hemolysis and cell death in human retinal pigmented epithelium (ARPE-19) cells) and a chemical approach by means of the α,α-diphenyl-β-picrylhydrazyl (DPPH) scavenging assay, using both electron paramagnetic resonance (EPR) spectroscopy and UV spectrophotometry. A computational approach was also used to investigate their potential primary mechanism of antioxidant action, as well as to rationalize the effect of functionalization on the nitrones reactivity toward DPPH, chosen as model radical in this study. Further insights were also gathered by exploring the nitrone electrochemical properties via cyclic voltammetry and by studying their kinetic behavior by means of EPR spectroscopy. Results showed that the introduction of an electron-withdrawing group in the phenyl moiety in the para position significantly increased the antioxidant capacity of benzoxazinic nitrones both in cell and cell-free systems. From the mechanistic point of view, the calculated results closely matched the experimental findings, strongly suggesting that the H-atom transfer (HAT) is likely to be the primary mechanism in the DPPH quenching.

scholarly journals Activity of Gatifloxacin in an In Vitro Pharmacokinetic-Pharmacodynamic Model against Staphylococcus aureus Strains either Susceptible to Ciprofloxacin or Exhibiting Various Levels and Mechanisms of Ciprofloxacin Resistance

2006 ◽  
Vol 50 (6) ◽  
pp. 1931-1936 ◽  
Author(s):  
Boubakar B. Ba ◽  
Corinne Arpin ◽  
Céline Vidaillac ◽  
Arnaud Chausse ◽  
Marie-Claude Saux ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Goodness Of Fit ◽  
Reference Strain ◽  
Pharmacodynamic Model ◽  
Bacterial Killing ◽  
Β Phase ◽  
Ciprofloxacin Resistance ◽  
Total Elimination ◽  
Gram Positive Cocci

ABSTRACT Gatifloxacin (GAT) is a new 8-methoxy fluoroquinolone with enhanced activity against gram-positive cocci. Its activity was studied in an in vitro pharmacokinetic-pharmacodynamic model against five Staphylococcus aureus strains, either susceptible to ciprofloxacin or exhibiting various levels and mechanisms of ciprofloxacin (CIP) resistance: the ATCC 25923 reference strain (MICs of CIP and GAT: 0.5 and 0.1 μg/ml, respectively), its efflux mutant SA-1 (16 and 0.5 μg/ml; mutation in the norA promoter region), and three clinical strains, Sa2102 (2 and 0.2 μg/ml), Sa2667 (4 and 0.5 μg/ml), and Sa2669 (16 and 1 μg/ml), carrying mutations in the grlA (Ser80Tyr or Phe) and gyrA (Ser84Ala) quinolone resistance-determining regions (QRDRs) for Sa2669. Plasmatic pharmacokinetic profiles after daily 1-h perfusion of 400 mg for 48 h were accurately simulated. Thus, mean maximum concentration of drug in serum values for the two administration intervals were 5.36 and 5.80 μg/ml, respectively, and the corresponding half-life at β-phase values were 8.68 and 7.80 h (goodness of fit coefficient, >0.98). Therapeutic concentrations of GAT allowed the complete eradication of the susceptible strain within 12 h (difference between the bacterial counts at the beginning of the treatment and at a defined time: −2.18 at the 1-h time point [t 1] and −6.80 at t 24 and t 48; the bacterial killing and regrowth curve from 0 to 48 h was 30.2 h × log CFU/milliliter). However, mutants (M) with GAT MICs increased by 4- to 40-fold were selected from the other strains. They acquired mutations either supplementary (MSa2102 and MSa2667) or different (Ala84Val for MSa2669) in gyrA or in both gyrA and grlA QRDRs (MSA-1). MSa2667 additionally overproduced efflux system(s) without norA promoter modification. Thus, GAT properties should allow the total elimination of ciprofloxacin-susceptible S. aureus, but resistant mutants might emerge from strains showing reduced susceptibility to older fluoroquinolones independently of the first-step mutation(s).

Characterization of lipopolysaccharide transport protein complex

2014 ◽  
Vol 9 (2) ◽  
pp. 131-138
Author(s):  
Quanju Xiang ◽  
Haiyan Wang ◽  
Zhongshan Wang ◽  
Yizheng Zhang ◽  
Changjiang Dong
Keyword(s):  
Transport Mechanism ◽  
Transport Proteins ◽  
Gram Negative Bacteria ◽  
Inner Membrane ◽  
Toxic Compounds ◽  
Outer Membranes ◽  
Harsh Conditions ◽  
Cytoplasmic Side

AbstractLipopolysaccharide (LPS) is an essential component of the outer membranes (OM) of most Gram-negative bacteria, which plays a crucial role in protection of the bacteria from toxic compounds and harsh conditions. The LPS is biosynthesized at the cytoplasmic side of inner membrane (IM), and then transported across the aqueous periplasmic compartment and assembled correctly at the outer membrane. This process is accomplished by seven LPS transport proteins (LptA-G), but the transport mechanism remains poorly understood. Here, we present findings by pull down assays in which the periplasmic component LptA interacts with both the IM complex LptBFGC and the OM complex LptDE in vitro, but not with complex LptBFG. Using purified Lpt proteins, we have successfully reconstituted the seven transport proteins as a complex in vitro. In addition, the LptC may play an essential role in regulating the conformation of LptBFG to secure the lipopolysaccharide from the inner membrane. Our results contribute to the understanding of lipopolysaccharide transport mechanism and will provide a platform to study the detailed mechanism of the LPS transport in vitro.

scholarly journals Evaluation of near-tropopause ozone distributions in the Global Modeling Initiative combined stratosphere/troposphere model with ozonesonde data

2008 ◽  
Vol 8 (1) ◽  
pp. 1589-1634 ◽  
Author(s):  
D. B. Considine ◽  
J. A. Logan ◽  
M. A. Olsen
Keyword(s):  
Annual Cycle ◽  
Transport Model ◽  
Model Simulation ◽  
Atmospheric Composition ◽  
Vertical Resolution ◽  
Residual Circulation ◽  
Vertical Diffusion ◽  
Global Modeling ◽  
Upper Troposphere ◽  
The Tropics

Abstract. The NASA Global Modeling Initiative has developed a combined stratosphere/troposphere chemistry and transport model which fully represents the processes governing atmospheric composition near the tropopause. We evaluate model ozone distributions near the tropopause, using two high vertical resolution monthly mean ozone profile climatologies constructed with ozonesonde data, one by averaging on pressure levels and the other relative to the thermal tropopause. Model ozone is high-biased at the SH tropical and NH midlatitude tropopause by ~45% in a 4° latitude × 5° longitude model simulation. Increasing the resolution to 2°×2.5&amp;deg increases the NH tropopause high bias to ~60%, but decreases the tropical tropopause bias to ~30%, an effect of a better-resolved residual circulation. The tropopause ozone biases appear not to be due to an overly vigorous residual circulation or excessive stratosphere/troposphere exchange, but are more likely due to insufficient vertical resolution or excessive vertical diffusion near the tropopause. In the upper troposphere and lower stratosphere, model/measurement intercomparisons are strongly affected by the averaging technique. NH and tropical mean model lower stratospheric biases are <20%. In the upper troposphere, the 2°×2.5&amp;deg simulation exhibits mean high biases of ~20% and~35% during April in the tropics and NH midlatitudes, respectively, compared to the pressure-averaged climatology. However, relative-to-tropopause averaging produces upper troposphere high biases of ~30% and 70% in the tropics and NH midlatitudes. This is because relative-to-tropopause averaging better preserves large cross-tropopause O3 gradients, which are seen in the daily sonde data, but not in daily model profiles. The relative annual cycle of ozone near the tropopause is reproduced very well in the model Northern Hemisphere midlatitudes. In the tropics, the model amplitude of the near-tropopause annual cycle is weak. This is likely due to the annual amplitude of mean vertical upwelling near the tropopause, which analysis suggests is ~30% weaker than in the real atmosphere.

A multifunctional poly(acrylic acid)/gelatin hydrogel

2009 ◽  
Vol 24 (5) ◽  
pp. 1653-1661 ◽  
Author(s):  
Qunwei Tang ◽  
Jihuai Wu ◽  
Jianming Lin ◽  
Shijun Fan ◽  
De Hu
Keyword(s):  
Acrylic Acid ◽  
Transport Model ◽  
Interpenetrating Network ◽  
Hybrid Hydrogel ◽  
Elongation At Break ◽  
Gelatin Hydrogel ◽  
Preparation Conditions ◽  
Aqueous Solution Polymerization ◽  
Poly Acrylic Acid

A poly(acrylic acid)/gelatin interpenetrating network hydrogel was synthesized by aqueous solution polymerization. The influences of preparation conditions including cross-linker, initiator, gelatin content, and neutralization degree on the swelling ratios of the hydrogels are investigated. The swelling, mechanical strength, biodegradability, and drug-release properties of poly(acrylic acid)/gelatin hydrogel are evaluated. The hydrogel has excellent mechanical properties; tensile strength is 1500 kPa, and elongation at break is 887%, respectively. The in vitro biodegradation shows that an interpenetrating network structure exists in the poly(acrylic acid)/gelatin hybrid hydrogel. A release study indicates that the theophylline release from the hydrogel depends on the cross-linking density of the hydrogel and pH of the medium, and the drug diffusion obeys an anomalous transport model.

Transport of amino acids by isolated gills of the mussel Mytilus californianus Conrad

1975 ◽  
Vol 62 (2) ◽  
pp. 313-325
Author(s):  
S. H. Wright ◽  
T. L. Johnson ◽  
J. H. Crowe
Keyword(s):  
Amino Acids ◽  
Significant Role ◽  
Transport Mechanism ◽  
Surrounding Medium ◽  
Gill Tissue ◽  
Mytilus Californianus ◽  
Animal Nutrition ◽  
Neutral Amino Acids ◽  
Kinetics Of

The unidirectional influx of cycloleucine into in vitro preparations of gill tissue of the mussel, Mytilus californianus, was determined. Influx was found to be linear for at least an hour, and the kinetics of cycloleucine influx conformed to Michaelis-Menten type kinetics. The transport mechanism(s) for cycloleucine is relatively specific for the L-enantiomorph of neutral amino acids, and is capable of accumulating cycloleucine to intracellular concentrations much higher than those of the surrounding medium. Evedence is presented that the transport of amino acids by gill tissue plays a significant role in whole animal nutrition.

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