Nano-engineering of ketorolac tromethamine platforms for ocular treatment of inflammatory disorders

Aim: The development and optimization of Ketorolac tromethamine-loaded polylactic-co-glycolic acid nanoparticles (KT-NPs) for the treatment of inflammatory processes of the eye. Materials & methods: KT-NPs were developed by factorial design and characterized by assessing their physicochemical properties. Biopharmaceutical behavior studies, ocular tolerance, anti-inflammatory efficacy and bioavailability tests were performed on pigs. Results: Optimized KT-NPs of 112 nm, narrow distribution with encapsulation efficiency near 100% were obtained. KT release followed the Weibull model and there was significantly greater retention in the cornea and sclera than in the commercial reference. KT-NPs showed no signs of ocular irritancy and similar anti-inflammatory efficacy to the commercial reference. Conclusion: KT-NPs were a suitable alternative for the treatment of inflammatory disorders of the anterior and posterior segments of the eye as an alternative to conventional topical formulations.

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Can emu oil ameliorate inflammatory disorders affecting the gastrointestinal system?

Australian Journal of Experimental Agriculture ◽

10.1071/ea08139 ◽

2008 ◽

Vol 48 (10) ◽

pp. 1276 ◽

Cited By ~ 7

Author(s):

Gordon S. Howarth ◽

Ruth J. Lindsay ◽

Ross N. Butler ◽

Mark S. Geier

Keyword(s):

Gastrointestinal Diseases ◽

Gastrointestinal System ◽

Adjunctive Treatment ◽

Viral Gastroenteritis ◽

Inflammatory Disorders ◽

Scientific Investigations ◽

Emu Oil ◽

Inflammatory Processes ◽

Anti Inflammatory

Emu oil possesses significant anti-inflammatory properties in vivo, primarily when applied topically. However, to date, the evidence supporting its therapeutic application has been largely anecdotal, and significant batch-to-batch variations in potency have been reported. Nevertheless, the anti-inflammatory properties of emu oil suggest therapeutic promise for the adjunctive treatment of a range of disparate gastrointestinal diseases and disorders characterised by inflammatory processes. These include the idiopathic condition inflammatory bowel disease, chemotherapy-induced mucositis, non-steroidal anti-inflammatory drug enteropathy and the various infective enteritides (i.e. fungal, bacterial and viral gastroenteritis). Although rigorous scientific investigations are in their infancy, the evidence for emu oil efficacy in extra-intestinal disorders, supported by limited in vivo investigations of other naturally sourced oils, identifies emu oil as a possible adjunct to conventional treatment approaches for inflammatory disorders affecting the gastrointestinal system.

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Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

Current Medicinal Chemistry ◽

10.2174/0929867326666191212102407 ◽

2020 ◽

Vol 28 (2) ◽

pp. 360-376 ◽

Cited By ~ 7

Author(s):

Atefeh Amiri ◽

Maryam Mahjoubin-Tehran ◽

Zatollah Asemi ◽

Alimohammad Shafiee ◽

Sarah Hajighadimi ◽

...

Keyword(s):

Molecular Mechanisms ◽

Antioxidant Activities ◽

Natural Compounds ◽

Therapeutic Effects ◽

Inflammatory Disorder ◽

Inflammatory Disorders ◽

Therapeutic Modalities ◽

Anti Cancer ◽

Current Therapies ◽

Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

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ROS Inhibitory Activity and Cytotoxicity Evaluation of Benzoyl, Acetyl, Alkyl Ester, and Sulfonate Ester Substituted Coumarin Derivatives

Medicinal Chemistry ◽

10.2174/1573406415666190826153001 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1099-1111

Author(s):

Uzma Salar ◽

Khalid M. Khan ◽

Almas Jabeen ◽

Aisha Faheem ◽

Farwa Naqvi ◽

...

Keyword(s):

Inhibitory Activity ◽

Antiinflammatory Drug ◽

Vital Role ◽

Alkyl Ester ◽

Flufenamic Acid ◽

Coumarin Derivatives ◽

Inflammatory Disorders ◽

Enhanced Chemiluminescence ◽

Anti Inflammatory ◽

Sulfonate Ester

Background: A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. Methods: A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. Results: Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 μM), 24 (IC50 = 41.8 ± 1.5 μM), 26 (IC50 = 10.6 ± 2.8 μM), 28 (IC50 = 20.9 ± 1.5 μM), and 41 (IC50 = 4.6 ± 0.3 μM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 μM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 μM), 14 (IC50 = 216.5 ± 6.2 μM), 16 (IC50 = 187.4 ± 2.2 μM), and 20 (IC50 = 196.2 ± 2.0 μM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring “R” played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 μM). Conclusion: Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.

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Development, Pre-clinical Investigation and Histopathological Evaluation of Metronidazole Loaded Topical Formulation for Treatment of Skin Inflammatory disorders

Drug Delivery Letters ◽

10.2174/2210303110999200821123047 ◽

2020 ◽

Vol 10 ◽

Author(s):

Divya Thakur ◽

Gurpreet Kaur ◽

Sheetu Wadhwa ◽

Ashana Puri

Keyword(s):

Ex Vivo ◽

Clinical Investigation ◽

In Vivo Studies ◽

Tween 20 ◽

Inflammatory Disorders ◽

Rat Paw Edema ◽

Ex Vivo Permeation ◽

Permeation Studies ◽

Anti Inflammatory

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at target site, which requires frequent administration and poor patient compliance. Objective: The aim of current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of surfactant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-psoriatic activity (mouse-tail test). Results: The particle size analyses revealed average diameter and polydispersity index of selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemulsion i.e. 21.90 ± 1.92 μg/cm2 which was 6.65 times higher as compared to Marketed gel (Metrogyl gel®) with 3.29 ± 0.11 μg/cm2 (p<0.05). The results of in vivo studies suggested the microemulsion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests efficacy of the developed MTZ loaded microemulsion in treatment of chronic skin inflammatory disorders.

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Micromechanical Punching: A Versatile Method for Non-Spherical Microparticle Fabrication

Polymers ◽

10.3390/polym13010083 ◽

2020 ◽

Vol 13 (1) ◽

pp. 83

Author(s):

Ritika Singh Petersen ◽

Anja Boisen ◽

Stephan Sylvest Keller

Keyword(s):

Drug Delivery ◽

High Resolution ◽

Physicochemical Properties ◽

High Throughput ◽

Liquid State ◽

Soft Lithography ◽

Glycolic Acid ◽

Thermosetting Polymers ◽

Spherical Microparticle ◽

Spherical Microparticles

Microparticles are ubiquitous in applications ranging from electronics and drug delivery to cosmetics and food. Conventionally, non-spherical microparticles in various materials with specific shapes, sizes, and physicochemical properties have been fabricated using cleanroom-free lithography techniques such as soft lithography and its high-resolution version particle replication in non-wetting template (PRINT). These methods process the particle material in its liquid/semi-liquid state by deformable molds, limiting the materials from which the particles and the molds can be fabricated. In this study, the microparticle material is exploited as a sheet placed on a deformable substrate, punched by a robust mold. Drawing inspiration from the macro-manufacturing technique of punching metallic sheets, Micromechanical Punching (MMP) is a high-throughput technique for fabrication of non-spherical microparticles. MMP allows production of microparticles from prepatterned, porous, and fibrous films, constituting thermoplastics and thermosetting polymers. As an illustration of application of MMP in drug delivery, flat, microdisk-shaped Furosemide embedded poly(lactic-co-glycolic acid) microparticles are fabricated and Furosemide release is observed. Thus, it is shown in the paper that Micromechanical punching has potential to make micro/nanofabrication more accessible to the research and industrial communities active in applications that require engineered particles.

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Controlled Nitric Oxide Release Using Poly(lactic-co-glycolic acid) Nanoparticles for Anti-Inflammatory Effects

Biomacromolecules ◽

10.1021/acs.biomac.0c01176 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4972-4979

Author(s):

Yoogyeong Oh ◽

Hyejoong Jeong ◽

Sungmin Lim ◽

Jinkee Hong

Keyword(s):

Nitric Oxide ◽

Glycolic Acid ◽

Nitric Oxide Release ◽

Anti Inflammatory

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Anti-inflammatory Effects of Plant-based Foods and of their Constituents

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.78.6.293 ◽

2008 ◽

Vol 78 (6) ◽

pp. 293-298 ◽

Cited By ~ 37

Author(s):

Bernhard Watzl

Keyword(s):

Cardiovascular Diseases ◽

Bioactive Compounds ◽

Pathological Condition ◽

Wide Spectrum ◽

Bioactive Constituents ◽

Plant Foods ◽

Whole Wheat ◽

Markers Of Inflammation ◽

Inflammatory Processes ◽

Anti Inflammatory

Inflammation is a pathological condition underlying a number of diseases including cardiovascular diseases, cancer, and chronic inflammatory diseases. In addition, healthy, obese subjects also express markers of inflammation in their blood. Diet provides a variety of nutrients as well as non-nutritive bioactive constituents which modulate immunomodulatory and inflammatory processes. Epidemiological data suggest that dietary patterns strongly affect inflammatory processes. Primarily the intake of fruit and vegetables as well as of whole wheat is inversely associated with the risk of inflammation. In addition to observational studies there are also data from human intervention studies suggesting an anti-inflammatory potential of these plant foods. At the level of bioactive compounds occurring in plant foods, primarily carotenoids and flavonoids seem to modulate inflammatory as well as immunological processes. In conclusion, there is convincing evidence that plant foods and non-nutritive constituents associated with these foods modulate immunological and inflammatory processes. By means of anti-inflammatory activities a plant-based diet may contribute to the lower risk of cardiovascular diseases and cancer. A high intake of vegetables, fruit, and whole wheat as recommended by all international nutrition authorities provides a wide spectrum of bioactive compounds at health-promoting concentrations.

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Anti-Inflammatory Properties of Diet: Role in Healthy Aging

Biomedicines ◽

10.3390/biomedicines9080922 ◽

2021 ◽

Vol 9 (8) ◽

pp. 922

Author(s):

Kristine Stromsnes ◽

Angela G. Correas ◽

Jenny Lehmann ◽

Juan Gambini ◽

Gloria Olaso-Gonzalez

Keyword(s):

Cardiovascular Disease ◽

Autoimmune Disease ◽

Neurological Disease ◽

Healthy Aging ◽

Dietary Guidelines ◽

The Body ◽

Inflammatory Activity ◽

Allergic Reactions ◽

Inflammatory Processes ◽

Anti Inflammatory

Inflammation is a physiological process involved in the defenses of the body and the repair of tissues. It is acutely activated by infections, trauma, toxins, or allergic reactions. However, if it becomes chronic, inflammation can end up stimulating the development of diseases such as cardiovascular disease, autoimmune disease, neurological disease, or cancer. Additionally, during aging, inflammation becomes increasingly more chronic. Furthermore, we found that certain foods, such as saturated fats, have pro-inflammatory activity. Taking this into account, in this review we have discussed different diets with possible anti-inflammatory activity, the commonly ingested components of each diet and their active compounds. In addition, we have proposed some dietary guidelines, as well as a list of compounds present in foods with anti-inflammatory activity, outlining how to combine them to achieve optimal anti-inflammatory effects. Therefore, we can conclude that the compounds in our diet with anti-inflammatory activity could help alleviate the inflammatory processes derived from diseases and unhealthy diets, and thereby promote healthy aging.

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