scholarly journals Optimization and Evaluation of the In Vitro Permeation Parameters of Topical Products with Non-Steroidal Anti-Inflammatory Drugs through Strat-M® Membrane

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1305
Author(s):  
Bartłomiej Milanowski ◽  
Hanna Wosicka-Frąckowiak ◽  
Eliza Główka ◽  
Małgorzata Sosnowska ◽  
Stanisław Woźny ◽  
...  
Keyword(s):  
Human Skin ◽  
Skin Barrier ◽  
Pharmaceutical Products ◽  
Topical Formulations ◽  
In Vitro Permeation ◽  
Diffusion Characteristics ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Spray Formulation

Pharmaceutical products containing non-steroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed topical formulations used for analgesic and antirheumatic properties. These drugs must overcome the skin barrier to cause a therapeutic effect. Human skin has been widely used as a model to study in vitro drug diffusion and permeation, however, it suffers from many limitations. Therefore, to perform in vitro permeation test (IVPT), we used a Strat-M® membrane with diffusion characteristics well-correlated to human skin. This study’s objective was to optimize the IVPT conditions using Plackett–Burman experimental design for bio-predictive evaluation of the in vitro permeation rates of five non-steroidal anti-inflammatory drugs (diclofenac, etofenamate, ibuprofen, ketoprofen, naproxen) across Strat-M® membrane from commercial topical formulations. The Plackett–Burman factorial design was used to screen the effect of seven factors in eight runs with one additional center point. This tool allowed us to set the sensitive and discriminative IVPT final conditions that can appropriately characterize the NSAIDs formulations. The permeation rate of etofenamate (ETF) across the Strat-M® membrane was 1.7–14.8 times faster than other NSAIDs from selected semisolids but 1.6 times slower than the ETF spray formulation.

In vitro Topical Delivery of Non-Steroidal Anti-inflammatory Drugs through Human Skin

2011 ◽  
Vol 49 (06) ◽  
pp. 509-513
Author(s):  
Claire-Marie Vincent ◽  
Cécile Laugel ◽  
Jean-Paul Marty
Keyword(s):  
Human Skin ◽  
Topical Delivery ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

In vitro and in vivo synergistic interactions between the flavonoid rutin with paracetamol and non-steroidal anti-inflammatory drugs

2021 ◽  
Author(s):  
Juan Ramón Zapata-Morales ◽  
Angel Josabad Alonso-Castro ◽  
Gloria Sarahí Muñoz-Martínez ◽  
María Mayela Martínez-Rodríguez ◽  
Mónica Esther Nambo-Arcos ◽  
...  
Keyword(s):  
Synergistic Interactions ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals Development and Evaluation of a Topical Anti-Inflammatory Preparation Containing Dodonaea polyandra Extract

2015 ◽  
Vol 18 (4) ◽  
pp. 578 ◽  
Author(s):  
Bradley S Simpson ◽  
Xianling Luo ◽  
Jiping Wang ◽  
Yunmei Song ◽  
David Claudie ◽  
...  
Keyword(s):  
Phase Separation ◽  
Human Skin ◽  
Dosage Form ◽  
Interleukin 1 ◽  
In Vitro Release ◽  
Skin Inflammation ◽  
Skin Model ◽  
Inflammation Model ◽  
Anti Inflammatory

Purpose: We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

In Vitro Chondrotoxicity of Nonsteroidal Anti-inflammatory Drugs and Opioid Medications

2017 ◽  
Vol 45 (14) ◽  
pp. 3345-3350 ◽  
Author(s):  
Geoffrey D. Abrams ◽  
Wenteh Chang ◽  
Jason L. Dragoo
Keyword(s):  
Cell Death ◽  
Single Dose ◽  
Joint Surface ◽  
Saline Control ◽  
Type I ◽  
Dose Equivalent ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Opioid Medications

Background: A variety of medications are administered to the intra-articular space for the relief of joint pain. While amide-type local anesthetics have been extensively studied, there is minimal information regarding the potential chondrotoxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid medications. Purpose: To investigate the in vitro chondrotoxicity of single-dose equivalent concentrations of ketorolac, morphine, meperidine, and fentanyl on human chondrocytes. Study Design: Controlled laboratory study. Methods: Human cartilage was arthroscopically harvested from the intercondylar notch and expanded in vitro. Gene expression of cultured chondrocytes before treatment was performed with quantitative polymerase chain reaction for type I collagen, type II collagen, aggrecan, and SOX9. Chondrocytes were then exposed to 0.01%, 0.02%, and 0.04% morphine sulfate; 0.3% and 0.6% ketorolac tromethamine; 0.5%, 1.0%, and 1.5% meperidine hydrochloride; 0.0005% and 0.001% fentanyl citrate; and saline. A custom bioreactor was used to constantly deliver medications, with the dosage of each medication and the duration of exposure based on standard dose equivalents, medication half-lives, and differences in the surface area between the 6-well plates and the native joint surface. After treatment, a live/dead assay was used to assess chondrocyte viability and if minimal cell death was detected. A subset of samples after treatment was maintained to analyze for possible delayed cell death. Results: All tested concentrations of ketorolac and meperidine caused significantly increased cell death versus the saline control, demonstrating a dose-response relationship. The morphine and fentanyl groups did not show increased chondrotoxicity compared with the saline group, even after 2 weeks of additional culture. Conclusion: In vitro exposure of chondrocytes to single-dose equivalent concentrations of either ketorolac or meperidine demonstrated significant chondrotoxicity, while exposure to morphine or fentanyl did not lead to increased cell death.

scholarly journals Antimicrobial Activity of Non-steroidal Anti-inflammatory Drugs on Biofilm: Current Evidence and Potential for Drug Repurposing

2021 ◽  
Vol 12 ◽  
Author(s):  
Rodrigo Cuiabano Paes Leme ◽  
Raquel Bandeira da Silva
Keyword(s):  
Bacterial Species ◽  
Drug Repurposing ◽  
Current Evidence ◽  
Pharmacokinetic Studies ◽  
Bacterial Populations ◽  
Human Pharmacokinetic ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

It has been demonstrated that some non-steroidal anti-inflammatory drugs (NSAIDs), like acetylsalicylic acid, diclofenac, and ibuprofen, have anti-biofilm activity in concentrations found in human pharmacokinetic studies, which could fuel an interest in repurposing these well tolerated drugs as adjunctive therapies for biofilm-related infections. Here we sought to review the currently available data on the anti-biofilm activity of NSAIDs and its relevance in a clinical context. We performed a systematic literature review to identify the most commonly tested NSAIDs drugs in the last 5 years, the bacterial species that have demonstrated to be responsive to their actions, and the emergence of resistance to these molecules. We found that most studies investigating NSAIDs’ activity against biofilms were in vitro, and frequently tested non-clinical bacterial isolates, which may not adequately represent the bacterial populations that cause clinically-relevant biofilm-related infections. Furthermore, studies concerning NSAIDs and antibiotic resistance are scarce, with divergent outcomes. Although the potential to use NSAIDs to control biofilm-related infections seems to be an exciting avenue, there is a paucity of studies that tested these drugs using appropriate in vivo models of biofilm infections or in controlled human clinical trials to support their repurposing as anti-biofilm agents.

scholarly journals Human iPSC-derived brain endothelial microvessels in a multi-well format enable permeability screens of anti-inflammatory drugs

2021 ◽  
Author(s):  
Sven Fengler ◽  
Birgit Kurkowsky ◽  
Sanjeev Kumar Kaushalya ◽  
Wera Roth ◽  
Philip Denner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neurodegenerative Diseases ◽  
Induced Pluripotent Stem Cell ◽  
Barrier Properties ◽  
Brain Diseases ◽  
Rapid Screening ◽  
Sodium Fluorescein ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Optimizing drug candidates for blood-brain barrier (BBB) penetration in humans remains one of the key challenges and many devastating brain diseases including neurodegenerative diseases still do not have adequate treatments. So far, it has been difficult to establish state-of-the-art human stem cell derived in vitro models that mimic physiological barrier properties including a 3D microvasculature in a format that is scalable enough to screen drugs for BBB penetration in early drug development phases. To address this challenge, we established human induced pluripotent stem cell (iPSC)-derived brain endothelial microvessels in a standardized and scalable multi-well plate format. iPSC-derived brain microvascular endothelial cells (BMECs) were supplemented with primary cell conditioned media and grew to intact microvessels in 10 days of culturing. Produced microvessels show a typical BBB phenotype including endothelial protein expression, tight-junctions and polarized localization of efflux transporter. Microvessels exhibited physiological relevant trans-endothelial electrical resistance (TEER), were leak tight for 10 kDa dextran-Alexa 647 and strongly limited the permeability of sodium fluorescein (NaF). Permeability tests with reference compounds confirmed the suitability of our model as platform to identify potential BBB penetrating anti-inflammatory drugs. In summary, the here presented brain microvessel platform recapitulates physiological properties and allows rapid screening of BBB permeable anti-inflammatory compounds that has been suggested as promising substances to cure so far untreatable neurodegenerative diseases.

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