Determination of trans-Resveratrol in Bio-Matrices for in Vitro, ex Vivo, and in Vivo Pharmacokinetic Studies by LC Spectrometric Analysis

2008 ◽  
Vol 68 (11-12) ◽  
pp. 1013-1019 ◽  
Author(s):  
Hui He ◽  
Xi J. Chen ◽  
Guang Ji Wang
Keyword(s):  
Ex Vivo ◽  
Spectrometric Analysis ◽  
Pharmacokinetic Studies

Detection of allergen-induced airway hyperresponsiveness in isolated mouse lungs

2006 ◽  
Vol 291 (3) ◽  
pp. L466-L472 ◽  
Author(s):  
Martin Witzenrath ◽  
Birgit Ahrens ◽  
Stefanie M. Kube ◽  
Armin Braun ◽  
Heinz G. Hoymann ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Ex Vivo ◽  
Whole Body ◽  
Strongly Correlated ◽  
Ex Vivo Model ◽  
Isolated Lungs ◽  
Spontaneously Breathing

Airway hyperresponsiveness (AHR) is a hallmark of bronchial asthma. Important features of this exaggerated response to bronchoconstrictive stimuli have mostly been investigated in vivo in intact animals or in vitro in isolated tracheal or bronchial tissues. Both approaches have important advantages but also certain limitations. Therefore, the aim of our study was to develop an ex vivo model of isolated lungs from sensitized mice for the investigation of airway responsiveness (AR). BALB/c mice were sensitized by intraperitoneal ovalbumin (Ova) and subsequently challenged by Ova inhalation. In vivo AR was measured in unrestrained animals by whole body plethysmography after stimulation with aerosolized methacholine (MCh) with determination of enhanced pause ( Penh). Twenty-four hours after each Penh measurement, airway resistance was continuously registered in isolated, perfused, and ventilated lungs on stimulation with inhaled or intravascular MCh or nebulized Ova. In a subset of experiments, in vivo AR was additionally measured in orotracheally intubated, spontaneously breathing mice 24 h after Penh measurement, and lungs were isolated further 24 h later. Isolated lungs of allergen-sensitized and -challenged mice showed increased AR after MCh inhalation or infusion as well as after specific provocation with aerosolized allergen. AR was increased on days 2 and 5 after Ova challenge and had returned to baseline on day 9. AHR in isolated lungs after aerosolized or intravascular MCh strongly correlated with in vivo AR. Pretreatment of isolated lungs with the β2-agonist fenoterol diminished AR. In conclusion, this model provides new opportunities to investigate mechanisms of AHR as well as pharmacological interventions on an intact organ level.

scholarly journals Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1640
Author(s):  
Sreeja C. Nair ◽  
Kollencheri Puthenveettil Vinayan ◽  
Sabitha Mangalathillam
Keyword(s):  
Drug Release ◽  
Olfactory Epithelium ◽  
Drug Transport ◽  
Ex Vivo ◽  
Medical Attention ◽  
Pharmacokinetic Studies ◽  
Phenytoin Sodium ◽  
Drug Solution

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.

scholarly journals A new sensitive HPLC/UV method for simultaneous determination of paclitaxel, sorafenib and omeprazole in standard solutions and spiked plasma: Application to in-vitro and in-vivo evaluation of paclitaxel polymeric nanoformulations

2021 ◽  
Vol 20 (9) ◽  
pp. 1949-1959
Author(s):  
Mirina Sakhi ◽  
Abad Khan ◽  
Ismail Khan ◽  
Zafar Iqbal ◽  
Sumaira Irum Khan ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Chromatographic Method ◽  
Pharmacokinetic Studies ◽  
Good Resolution ◽  
In Vivo Evaluation ◽  
Spiked Plasma ◽  
Standard Solutions

Purpose: To develop a simple, novel, sensitive and rapid reverse phase high performance liquid chromatographic method for simultaneous determination of paclitaxel, sorafenib and omeprazole in standard solutions and spiked human plasma and its application to the in-vitro and in-vivo evaluation of paclitaxel polymeric nanoparticle formulations.Methods: The method was tested for the assessment of paclitaxel, omeprazole and sorafenib using tamoxifen citrate as internal standard. The analysis was performed at a wavelength of 235 nm using Thermo HS C18 column, 40 °C column oven temperature, acetonitrile and water (70:30 v/v, pH 3.37 adjusted with phosphoric acid) as a mobile phase and at a flow rate of 0.8 ml/min. All analytes were extracted by simple protein precipitation method using acetonitrile. The linearity was assessed in the concentration range of 1 - 2000 ng/mL for paclitaxel, omeprazole and sorafenib.Results: The developed chromatographic method effectively separated omeprazole, paclitaxel, sorafenib and IS with retention time of 3.93, 5.18, 6.43 and 9.93 min, respectively. The chromatograms of the three target compounds and IS showed good resolution and peak separation. The LOD of the method was 1, 5 and. 5 ng/mL while the LOQ was 2, 7.5 and 10 ng/mL, for paclitaxel, sorafenib and omeprazole, respectively.Conclusion: The proposed RP-HPLC–UV method for the assessment of paclitaxel, sorafenib and omeprazole in standard solutions and spiked plasma is simple, economical, sensitive and robust. The method is also suitable for the analysis of paclitaxel in nanoformulations and for its pharmacokinetic studies in an animal model.

scholarly journals Comparative study of the stabilities of synthetic in vitro and natural ex vivo transthyretin amyloid fibrils

2020 ◽  
Vol 295 (33) ◽  
pp. 11379-11387 ◽  
Author(s):  
Sara Raimondi ◽  
P. Patrizia Mangione ◽  
Guglielmo Verona ◽  
Diana Canetti ◽  
Paola Nocerino ◽  
...  
Keyword(s):  
Thermodynamic Stability ◽  
Amyloid Fibrils ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Biochemical Properties ◽  
Amyloid Formation ◽  
Free Energies

Systemic amyloidosis caused by extracellular deposition of insoluble fibrils derived from the pathological aggregation of circulating proteins, such as transthyretin, is a severe and usually fatal condition. Elucidation of the molecular pathogenic mechanism of the disease and discovery of effective therapies still represents a challenging medical issue. The in vitro preparation of amyloid fibrils that exhibit structural and biochemical properties closely similar to those of natural fibrils is central to improving our understanding of the biophysical basis of amyloid formation in vivo and may offer an important tool for drug discovery. Here, we compared the morphology and thermodynamic stability of natural transthyretin fibrils with those of fibrils generated in vitro either using the common acidification procedure or primed by limited selective cleavage by plasmin. The free energies for fibril formation were −12.36, −8.10, and −10.61 kcal mol−1, respectively. The fibrils generated via plasmin cleavage were more stable than those prepared at low pH and were thermodynamically and morphologically similar to natural fibrils extracted from human amyloidotic tissue. Determination of thermodynamic stability is an important tool that is complementary to other methods of structural comparison between ex vivo fibrils and fibrils generated in vitro. Our finding that fibrils created via an in vitro amyloidogenic pathway are structurally similar to ex vivo human amyloid fibrils does not necessarily establish that the fibrillogenic pathway is the same for both, but it narrows the current knowledge gap between in vitro models and in vivo pathophysiology.

scholarly journals FORMULATION AND OPTIMIZATION OF QUERCETIN LOADED NANOSPONGES TOPICAL GEL: EX VIVO, PHARMACODYNAMIC AND PHARMACOKINETIC STUDIES

2019 ◽  
pp. 156-165
Author(s):  
Y. SARAH SUJITHA ◽  
Y. INDIRA MUZIB
Keyword(s):  
Particle Size ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Hydroxypropyl Methylcellulose ◽  
Entrapment Efficiency ◽  
Diffusion Method ◽  
Pharmacokinetic Studies ◽  
Topical Gel

Objective: Quercetin is therapeutically hampered because of its poor solubility. The present investigation was aimed to prepare quercetin loaded nanosponges topical gel to enhance the solubility and efficacy of the drug. Methods: Quercetin nanosponges were prepared by emulsion solvent diffusion method. Developed nanosponges optimized by particle size, SEM, entrapment efficiency, FT-IR, DSC, P-XRD, In vitro studies. The optimized formulation of nanosponges was loaded into a topical gel and it was characterized by ex-vivo, in vivo Pharmacodynamic and kinetic studies. Results: The particle size and zeta potential of optimized nanosponges were found to be 188.3 nm and-0.1mV. Surface morphology was studied using SEM Analysis which showed tiny sponge-like structure and entrapment efficiency was found to be 96.5 %. In vitro drug release of optimized nanosponges was found to be 98.6% for 7hours. Optimized nanosponges entrapped gel was prepared by using carbopol 934 and hydroxypropyl methylcellulose as gelling agents. The prepared nanogels were homogenous and ex-vivo skin permeation studies of the optimized nanosponges gel was found to be 98.1% for 5 h, quercetin loaded nanosponges has shown higher skin permeation efficiency (18.4µg/cm2±2.1) compared to pure quercetin gel. The pharmacokinetic and pharmacodynamic studies showed that the quercetin loaded nanosponges has shown more effective when compared to marketed formulation. Conclusion: Quercetin loaded nanosponges gel has shown a significant increase in activity (p<0.05) compared to the marketed formulation (Voveran Emulgel).

scholarly journals A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma

2021 ◽  
Author(s):  
Oscar Maiques ◽  
Bruce Fanshawe ◽  
Eva Crosas-Molist ◽  
Irene Rodriguez-Hernandez ◽  
Alessia Volpe ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Myosin Ii ◽  
Digital Pathology ◽  
Rho Kinase ◽  
Spectrometric Analysis ◽  
Melanoma Metastasis ◽  
Melanoma Model ◽  
Metastasis Model

Abstract Background Metastasis is a hallmark of cancer and responsible for most cancer deaths. Migrastatics were defined as drugs interfering with all modes of cancer cell invasion and thus cancers’ ability to metastasise. First anti-metastatic treatments have recently been approved. Methods We used bioinformatic analyses of publicly available melanoma databases. Experimentally, we performed in vitro target validation (including 2.5D cell morphology analysis and mass spectrometric analysis of RhoA binding partners), developed a new traceable spontaneously metastasising murine melanoma model for in vivo validation, and employed histology (haematoxylin/eosin and phospho-myosin II staining) to confirm drug action in harvested tumour tissues. Results Unbiased and targeted bioinformatic analyses identified the Rho kinase (ROCK)-myosin II pathway and its various components as potentially relevant targets in melanoma. In vitro validation demonstrated redundancy of several RhoGEFs upstream of RhoA and confirmed ROCK as a druggable target downstream of RhoA. The anti-metastatic effects of two ROCK inhibitors were demonstrated through in vivo melanoma metastasis tracking and inhibitor effects also confirmed ex vivo by digital pathology. Conclusions We proposed a migrastatic drug development pipeline. As part of the pipeline, we provide a new traceable spontaneous melanoma metastasis model for in vivo quantification of metastasis and anti-metastatic effects by non-invasive imaging.

scholarly journals Cloud-Point Extraction Combined with Liquid Chromatography for the Determination of Ergosterol, a Natural Product with Diuretic Activity, in Rat Plasma, Urine, and Faeces

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Dan-Qian Chen ◽  
Jun-Min An ◽  
Ya-Long Feng ◽  
Ting Tian ◽  
Xiang-Yang Qin ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Cloud Point ◽  
Cloud Point Extraction ◽  
Rat Plasma ◽  
Ionic Surfactant ◽  
Pharmacokinetic Studies ◽  
Triton X

Ergosterol from many medicinal fungi has been demonstrated to possess a variety of pharmacological activitiesin vivoandin vitro. A new method based on cloud-point extraction has been developed, optimized and validated for the determination of ergosterol in rat plasma, urine and faeces by liquid chromatography. The non-ionic surfactant Triton X-114 was chosen as the extract solvent. The chromatographic separation was performed on an Inertsil ODS-3 analytical column with a mobile phase consisting of methanol and water (98 : 2, v/v) at a flow rate of 1 mL/min. The methodology was validated completely. The results indicated good performance in terms of specificity, linearity, detection and quantification limits, precision and accuracy. The method was successfully applied to the pharmacokinetic studies of ergosterol in rats. The results indicate that the ergosterol levels in feces are much higher than those in plasma and urine of the rat.

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