Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 

Saved Queries

Sign in to use this feature.

Search Filter Reset All

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
Add Subjects Reset
Select Subjects

Journals

remove_circle_outline
remove_circle_outline
Add Journals Reset
Select Journals

Article Types

remove_circle_outline
remove_circle_outline
Add Article Types Reset
Select Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
Add Countries / Regions Reset
Select Countries / Regions
Update Search
share announcement

Search Results (5)

Search Parameters:
Keywords = open flow microperfusion

Order results
Result details
Results per page
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
11 pages, 1943 KB  
Article
Topical Delivery Systems Effectively Transport Analgesics to Areas of Localized Pain via Direct Diffusion
by Thomas Birngruber, Kip Vought, Simon Schwingenschuh, Peter Reisenegger, Howard Maibach and Dmitri Lissin
Pharmaceutics 2023, 15(11), 2563; https://doi.org/10.3390/pharmaceutics15112563 - 31 Oct 2023
Cited by 4 | Viewed by 3009
Abstract
Topical delivery systems (TDSs) enable the direct transport of analgesics into areas of localized pain and thus minimize the side effects of administration routes that rely on systemic drug distribution. For musculoskeletal pain, clinicians frequently prescribe topical products containing lidocaine or diclofenac. This [...] Read more.
Topical delivery systems (TDSs) enable the direct transport of analgesics into areas of localized pain and thus minimize the side effects of administration routes that rely on systemic drug distribution. For musculoskeletal pain, clinicians frequently prescribe topical products containing lidocaine or diclofenac. This study assessed whether drug delivery from a TDS into muscle tissue occurs mainly via direct diffusion or systemic transport. An investigational TDS containing 108 mg lidocaine (SP-103, 5.4% lidocaine), a commercially available TDS containing 36 mg lidocaine (ZTlido®, 1.8% lidocaine), and a topical pain relief gel (Pennsaid®, 2% diclofenac) were tested. Using open flow microperfusion (OFM), interstitial fluid from the dermis, subcutaneous adipose tissue (SAT), and muscle was continuously sampled to assess drug penetration in all tissue layers. Ex vivo and in vivo experiments showed a higher diffusive transport of lidocaine compared to diclofenac. The data showed a clear contribution of diffusive transport to lidocaine concentration, with SP-103 5.4% resulting in a significantly higher lidocaine concentration in muscle tissue than commercially available ZTlido® (p = 0.008). These results indicate that SP-103 5.4% is highly effective in delivering lidocaine into muscle tissue in areas of localized pain for the treatment of musculoskeletal pain disorders (e.g., lower back pain). Full article
(This article belongs to the Special Issue Advances in Topical and Transdermal Drug Delivery, 2nd Edition)
►▼ Show Figures

Graphical abstract

14 pages, 1959 KB  
Article
Quantification of the Therapeutic Antibody Ocrelizumab in Mouse Brain Interstitial Fluid Using Cerebral Open Flow Microperfusion and Simultaneous Monitoring of the Blood–Brain Barrier Integrity
by Thomas Altendorfer-Kroath, Joanna Hummer, Denise Kollmann, Beate Boulgaropoulos, Reingard Raml and Thomas Birngruber
Pharmaceutics 2023, 15(7), 1880; https://doi.org/10.3390/pharmaceutics15071880 - 4 Jul 2023
Cited by 3 | Viewed by 3385
Abstract
The increasing relevance of improved therapeutic monoclonal antibodies (mAbs) to treat neurodegenerative diseases has strengthened the need to reliably measure their brain pharmacokinetic (PK) profiles. The aim of this study was, therefore, to absolutely quantify the therapeutic antibody ocrelizumab (OCR) as a model [...] Read more.
The increasing relevance of improved therapeutic monoclonal antibodies (mAbs) to treat neurodegenerative diseases has strengthened the need to reliably measure their brain pharmacokinetic (PK) profiles. The aim of this study was, therefore, to absolutely quantify the therapeutic antibody ocrelizumab (OCR) as a model antibody in mouse brain interstitial fluid (ISF), and to record its PK profile by using cerebral open flow microperfusion (cOFM). Further, to monitor the blood–brain barrier (BBB) integrity using an endogenous antibody with a similar molecular size as OCR. The study was conducted on 13 male mice. Direct and absolute OCR quantification was performed with cOFM in combination with zero flow rate, and subsequent bioanalysis of the obtained cerebral ISF samples. For PK profile recording, cerebral ISF samples were collected bi-hourly, and brain tissue and plasma were collected once at the end of the sampling period. The BBB integrity was monitored during the entire PK profile recording by using endogenous mouse immunoglobulin G1. We directly and absolutely quantified OCR and recorded its brain PK profile over 96 h. The BBB remained intact during the PK profile recording. The resulting data provide the basis for reliable PK assessment of therapeutic antibodies in the brain thus favoring the further development of therapeutic monoclonal antibodies. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
►▼ Show Figures

Graphical abstract

13 pages, 7471 KB  
Article
Advanced Online Monitoring of In Vitro Human 3D Full-Thickness Skin Equivalents
by Roland Schaller-Ammann, Sebastian Kreß, Jürgen Feiel, Gerd Schwagerle, Joachim Priedl, Thomas Birngruber, Cornelia Kasper and Dominik Egger
Pharmaceutics 2022, 14(7), 1436; https://doi.org/10.3390/pharmaceutics14071436 - 8 Jul 2022
Cited by 2 | Viewed by 3456
Abstract
Skin equivalents and skin explants are widely used for dermal penetration studies in the pharmacological development of drugs. Environmental parameters, such as the incubation and culture conditions affect cellular responses and thus the relevance of the experimental outcome. However, available systems such as [...] Read more.
Skin equivalents and skin explants are widely used for dermal penetration studies in the pharmacological development of drugs. Environmental parameters, such as the incubation and culture conditions affect cellular responses and thus the relevance of the experimental outcome. However, available systems such as the Franz diffusion chamber, only measure in the receiving culture medium, rather than assessing the actual conditions for cells in the tissue. We developed a sampling design that combines open flow microperfusion (OFM) sampling technology for continuous concentration measurements directly in the tissue with microfluidic biosensors for online monitoring of culture parameters. We tested our design with real-time measurements of oxygen, glucose, lactate, and pH in full-thickness skin equivalent and skin explants. Furthermore, we compared dermal penetration for acyclovir, lidocaine, and diclofenac in skin equivalents and skin explants. We observed differences in oxygen, glucose, and drug concentrations in skin equivalents compared to the respective culture medium and to skin explants. Full article
(This article belongs to the Special Issue Innovative In Vitro/In Silico Approaches to Drug Permeation and Absorption: The Highway to Implement the 3Rs Principles in Drug Development)
►▼ Show Figures

Figure 1

20 pages, 1469 KB  
Review
Current Approaches to Monitor Macromolecules Directly from the Cerebral Interstitial Fluid
by Marie-Laure Custers, Liam Nestor, Dimitri De Bundel, Ann Van Eeckhaut and Ilse Smolders
Pharmaceutics 2022, 14(5), 1051; https://doi.org/10.3390/pharmaceutics14051051 - 13 May 2022
Cited by 11 | Viewed by 4745
Abstract
Gaining insights into the pharmacokinetic and pharmacodynamic properties of lead compounds is crucial during drug development processes. When it comes to the treatment of brain diseases, collecting information at the site of action is challenging. There are only a few techniques available that [...] Read more.
Gaining insights into the pharmacokinetic and pharmacodynamic properties of lead compounds is crucial during drug development processes. When it comes to the treatment of brain diseases, collecting information at the site of action is challenging. There are only a few techniques available that allow for the direct sampling from the cerebral interstitial space. This review concerns the applicability of microdialysis and other approaches, such as cerebral open flow microperfusion and electrochemical biosensors, to monitor macromolecules (neuropeptides, proteins, …) in the brain. Microdialysis and cerebral open flow microperfusion can also be used to locally apply molecules at the same time at the site of sampling. Innovations in the field are discussed, together with the pitfalls. Moreover, the ‘nuts and bolts’ of the techniques and the current research gaps are addressed. The implementation of these techniques could help to improve drug development of brain-targeted drugs. Full article
(This article belongs to the Special Issue Brain-Targeted Drug Delivery)
►▼ Show Figures

Figure 1

14 pages, 2206 KB  
Article
Innovative Platform for the Advanced Online Monitoring of Three-Dimensional Cells and Tissue Cultures
by Sebastian Kreß, Roland Schaller-Ammann, Jürgen Feiel, Joachim Wegener, Joachim Priedl, Wolf Dietrich, Cornelia Kasper and Dominik Egger
Cells 2022, 11(3), 412; https://doi.org/10.3390/cells11030412 - 25 Jan 2022
Cited by 9 | Viewed by 5221
Abstract
The use of 3D cell cultures has gained increasing importance in medical and pharmaceutical research. However, the analysis of the culture medium is hardly representative for the culture conditions within a 3D model which hinders the standardization of 3D cultures and translation of [...] Read more.
The use of 3D cell cultures has gained increasing importance in medical and pharmaceutical research. However, the analysis of the culture medium is hardly representative for the culture conditions within a 3D model which hinders the standardization of 3D cultures and translation of results. Therefore, we developed a modular monitoring platform combining a perfusion bioreactor with an integrated minimally invasive sampling system and implemented sensors that enables the online monitoring of culture parameters and medium compounds within 3D cultures. As a proof-of-concept, primary cells as well as cell lines were cultured on a collagen or gelatin methacryloyl (GelMA) hydrogel matrix, while monitoring relevant culture parameters and analytes. Comparing the interstitial fluid of the 3D models versus the corresponding culture medium, we found considerable differences in the concentrations of several analytes. These results clearly demonstrate that analyses of the culture medium only are not relevant for the development of standardized 3D culture processes. The presented bioreactor with an integrated sampling and sensor platform opens new horizons for the development, optimization, and standardization of 3D cultures. Furthermore, this technology holds the potential to reduce animal studies and improve the transferability of pharmaceutical in vitro studies by gaining more relevant results, bridging the gap towards clinical translation. Full article
(This article belongs to the Collection Advances in Cell Culture and Tissue Engineering)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying article 1-50 on page 1 of 1.
Back to TopTop