Proof of concept testing of a positive reference material for in vivo and in vitro skin irritation testing

2017 ◽  
Vol 106 (8) ◽  
pp. 2807-2814 ◽  
Author(s):  
Yusuke Nomura ◽  
Michelle Lee ◽  
Chie Fukui ◽  
Kayo Watanabe ◽  
Daniel Olsen ◽  
...  
Keyword(s):  
Reference Material ◽  
Skin Irritation ◽  
Proof Of Concept

scholarly journals FORMULATION AND IN VITRO, IN VIVO EVALUATION OF PRONIOSOMAL GEL OF NEOMYCIN SULPHATE

2019 ◽  
pp. 156-163
Author(s):  
AMOL SHETE ◽  
PRIYANKA THORAT ◽  
RAJENDRA DOIJAD ◽  
SACHIN SAJANE
Keyword(s):  
Phase Separation ◽  
Skin Irritation ◽  
Entrapment Efficiency ◽  
Separation Method ◽  
Gelling Agent ◽  
In Vivo Evaluation ◽  
Skin Delivery ◽  
Span 60

Objective: The objectives of present investigation were to prepare and evaluate proniosomes of neomycin sulphate (NS) by coacervation phase separation method by using sorbitan monostearate (span 60) and lecithin as a surfactant to increase the penetration through the skin and study the effect of concentration of the same. Methods: Proniosomes of neomycin sulphate (NS) were prepared by coacervation phase separation method by using span 60 and lecithin. The effect of concentration of span 60 and lecithin was studied by factorial design. The prepared proniosomes were converted to gel by using carbopol as a gelling agent. The prepared formulations were evaluated for entrapment efficiency, in vitro drug diffusion, in vitro antibacterial activity and in vivo skin irritation test etc. Results: All Formulation showed the percentage entrapment efficiency in the range 38.31±0.05% to 77.96±0.06%, good homogeneity and gel was easily spreadable with minimal of shear. Optimized formulation showed enhanced rate of diffusion in vitro, increase in zone of inhibition against staphylococcus aureus, no skin irritation and showed good stability. Conclusion: The results of present study indicates that proniosomal gel formulated by using combination of span 60, Lecithin, cholesterol can be used to enhance skin delivery of NS because of excellent permeation of drug. Developed proniosomal gel formulation was promising carrier for NS

scholarly journals An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Gheed Al-Hity ◽  
FengWei Yang ◽  
Eduard Campillo-Funollet ◽  
Andrew E. Greenstein ◽  
Hazel Hunt ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
In Vitro Models ◽  
Proof Of Concept ◽  
Culture Model ◽  
Spheroid Growth ◽  
Confocal Images ◽  
Cancer Spheroids

AbstractInvestigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design.

scholarly journals Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 549
Author(s):  
Laura Garcia-Perez ◽  
Anita Ordas ◽  
Kirsten Canté-Barrett ◽  
Pauline Meij ◽  
Karin Pike-Overzet ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Severe Combined Immunodeficiency ◽  
Good Manufacturing Practice ◽  
Proof Of Concept ◽  
Preclinical Development ◽  
Hematopoietic Stem ◽  
Immune Deficiencies ◽  
Suitable Vector

Recent clinical trials using patient’s own corrected hematopoietic stem cells (HSCs), such as for primary immunodeficiencies (Adenosine deaminase (ADA) deficiency, X-linked Severe Combined Immunodeficiency (SCID), X-linked chronic granulomatous disease (CGD), Wiskott–Aldrich Syndrome (WAS)), have yielded promising results in the clinic; endorsing gene therapy to become standard therapy for a number of diseases. However, the journey to achieve such a successful therapy is not easy, and several challenges have to be overcome. In this review, we will address several different challenges in the development of gene therapy for immune deficiencies using our own experience with Recombinase-activating gene 1 (RAG1) SCID as an example. We will discuss product development (targeting of the therapeutic cells and choice of a suitable vector and delivery method), the proof-of-concept (in vitro and in vivo efficacy, toxicology, and safety), and the final release steps to the clinic (scaling up, good manufacturing practice (GMP) procedures/protocols and regulatory hurdles).

scholarly journals Apohemoglobin-haptoglobin complex attenuates the pathobiology of circulating acellular hemoglobin and heme

2020 ◽  
Vol 318 (5) ◽  
pp. H1296-H1307 ◽  
Author(s):  
Carlos J. Munoz ◽  
Ivan S. Pires ◽  
Jin Hyen Baek ◽  
Paul W. Buehler ◽  
Andre F. Palmer ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Capillary Density ◽  
Microvascular Blood Flow ◽  
Systemic Hypertension ◽  
Proof Of Concept ◽  
Heme Transfer ◽  
Ligand Transfer ◽  
Novel Therapeutic

This study highlights the apoHb-Hp complex as a novel therapeutic strategy to attenuate the adverse systemic and microvascular responses to intravascular Hb and heme exposure. In vitro and in vivo Hb exchange and heme transfer experiments demonstrated proof-of-concept Hb/heme ligand transfer to apoHb-Hp. The apoHb-Hp complex reverses Hb- and heme-induced systemic hypertension and microvascular vasoconstriction, preserves microvascular blood flow, and functional capillary density. In summary, the unique properties of the apoHb-Hp complex prevent adverse systemic and microvascular responses to Hb and heme-albumin exposure and introduce a novel therapeutic approach to facilitate simultaneous removal of extracellular Hb and heme.

scholarly journals CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Junjie Xu ◽  
Lin Ji ◽  
Yuelong Liang ◽  
Zhe Wan ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nuclear Interaction ◽  
Circular Rna ◽  
Advanced Hepatocellular Carcinoma ◽  
Proof Of Concept ◽  
Potential Strategy ◽  
Oncogenic Protein ◽  
Hcc Cells

AbstractSorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma (HCC). However, sorafenib resistance significantly limits its therapeutic efficacy, and the mechanisms underlying resistance have not been fully clarified. Here we report that a circular RNA, circRNA-SORE (a circular RNA upregulated in sorafenib-resistant HCC cells), plays a significant role in sorafenib resistance in HCC. We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib. Further studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm, which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 degradation. Moreover, our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells. Using different HCC mouse models, we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance. Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.

Diagnostic and Experimental Methods Skin irritation: tests in vivo and in vitro

1990 ◽  
Vol 23 (4) ◽  
pp. 287-287
Author(s):  
D. P. Bruynzeel ◽  
B. A. M. Gerritsen ◽  
P. De Haan ◽  
E. M. De Boer
Keyword(s):  
Skin Irritation ◽  
Experimental Methods

scholarly journals Proof of concept of a multimodal intravital molecular imaging system for tumour transpathology investigation

2021 ◽  
Author(s):  
Zhen Liu ◽  
Tao Cheng ◽  
Stephan Düwel ◽  
Ziying Jian ◽  
Geoffrey J. Topping ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Imaging System ◽  
Ex Vivo ◽  
Fiducial Markers ◽  
Proof Of Concept ◽  
Registration Accuracy ◽  
Microscopic Imaging ◽  
Window Chamber

Abstract Background Transpathology highlights the interpretation of the underlying physiology behind molecular imaging. However, it remains challenging due to the discrepancies between in vivo and in vitro measurements and difficulties of precise co-registration between trans-scaled images. This study aims to develop a multimodal intravital molecular imaging (MIMI) system as a tool for in vivo tumour transpathology investigation. Methods The proposed MIMI system integrates high-resolution positron imaging, magnetic resonance imaging (MRI) and microscopic imaging on a dorsal skin window chamber on an athymic nude rat. The window chamber frame was designed to be compatible with multimodal imaging and its fiducial markers were customized for precise physical alignment among modalities. The co-registration accuracy was evaluated based on phantoms with thin catheters. For proof of concept, tumour models of the human colorectal adenocarcinoma cell line HT-29 were imaged. The tissue within the window chamber was sectioned, fixed and haematoxylin–eosin (HE) stained for comparison with multimodal in vivo imaging. Results The final MIMI system had a maximum field of view (FOV) of 18 mm × 18 mm. Using the fiducial markers and the tubing phantom, the co-registration errors are 0.18 ± 0.27 mm between MRI and positron imaging, 0.19 ± 0.22 mm between positron imaging and microscopic imaging and 0.15 ± 0.27 mm between MRI and microscopic imaging. A pilot test demonstrated that the MIMI system provides an integrative visualization of the tumour anatomy, vasculatures and metabolism of the in vivo tumour microenvironment, which was consistent with ex vivo pathology. Conclusions The established multimodal intravital imaging system provided a co-registered in vivo platform for trans-scale and transparent investigation of the underlying pathology behind imaging, which has the potential to enhance the translation of molecular imaging.

scholarly journals Su1819 – New Class of Anti-Inflammatory Therapeutics Based on Gold (III) Complexes in Intestinal Inflammation – Proof of Concept Based on in Vitro and in Vivo Studies

2019 ◽  
Vol 156 (6) ◽  
pp. S-623
Author(s):  
Julia B. Krajewska ◽  
Jakub Wlodarczyk ◽  
Przemyslaw Taciak ◽  
Remigiusz Szczepaniak ◽  
Jakub Fichna
Keyword(s):  
Intestinal Inflammation ◽  
In Vivo Studies ◽  
Proof Of Concept ◽  
New Class ◽  
Anti Inflammatory

scholarly journals Improved Biosafety and Transdermal Delivery of Aconitine via Diethylene Glycol Monoethyl Ether-Mediated Microemulsion Assisted with Microneedles

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 163 ◽  
Author(s):  
Yongtai Zhang ◽  
Hongmei Hu ◽  
Qian Jing ◽  
Zhi Wang ◽  
Zehui He ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Diethylene Glycol ◽  
Transdermal Drug Delivery ◽  
Skin Irritation ◽  
In Vivo Microdialysis ◽  
Monoethyl Ether ◽  
Glycol Monoethyl Ether ◽  
Diethylene Glycol Monoethyl Ether

In the current study, diethylene glycol monoethyl ether-mediated microemulsions were combined with microneedles for enhanced transdermal aconitine delivery. The oil-in-water microemulsion increasedaconitine solubility and enhanced transdermal drug delivery and assistance with metal microneedles enhanced permeation of the aconitine-loaded microemulsion. Carried by the microemulsion, the in vitro permeability of aconitine was significantly enhanced, and further improved using microneedles. In vivo microdialysis revealed that the subcutaneous local drug concentration reached a high level within 30 min and remained relatively consistent to the end of the experimental period. AUC0-t of the microemulsion group was significantly higher than that of the aqueous solution group, and the microemulsion combined with microneedles group achieved the highest AUC0-t among the tested groups. The microemulsion and microdialysis probe also showed good biocompatibility with skin tissue. The microemulsion could be internalized by HaCaT and CCC-ESF-1 cells via lysosomes. The in vitro cytotoxicity of aconitine toward skin cells was reduced via encapsulation by microemulsion, and the prepared microemulsion developed no skin irritation. Hence, transdermal aconitine delivery and drug biosafety were effectively improved by loading into the microemulsion and assisting with microneedles, and in vivo microdialysis technique is suitable for realtime monitoring of transdermal drug delivery with microemulsion-based drug vehicles.

scholarly journals Small Molecule Inhibitor of Type Three Secretion Suppresses Acute and ChronicChlamydia trachomatisInfection in a Novel Urogenital Chlamydia Model

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ekaterina A. Koroleva ◽  
Natalia V. Kobets ◽  
Egor S. Zayakin ◽  
Sergei I. Luyksaar ◽  
Ludmila A. Shabalina ◽  
...  
Keyword(s):  
Genital Tract ◽  
Early Stage ◽  
Proof Of Concept ◽  
Ascending Infection ◽  
Molecule Inhibitor ◽  
Vaginal Secretions ◽  
Infection And Inflammation ◽  
Type Three Secretion

Previously, we reported that a compound from a group of thiohydrazides of oxamic acids, CL-55, possessed antichlamydial activityin vitrothat was accompanied by a decreased translocation of the type three secretion effector, IncA, into the host cell. In this study, the antichlamydial activity of CL-55 was testedin vivoin DBA/2 mice infected withC. trachomatisserovar D. We found that intravaginal inoculation of DBA/2 mice with the clinically relevant strain,C. trachomatisserovar D, results in a course of infection and pathology similar to that observed in humans. The early stage of infection in this model was characterized by a shedding ofChlamydiain vaginal secretions followed by an ascending infection and inflammation in the upper genital tract. We found that CL-55 possessed antibacterial activityin vivoand was able to controlC. trachomatisvaginal shedding, ascending infection, and inflammation in the upper genital organs in DBA/2 mice. Our data provide a proof of concept for the protective effect of the thiadiazinon, CL-55, against chlamydial infectionin vivoand support the feasibility of further studies of its potential therapeutic applications.

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