The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.
- MeSH
- Acrylamides chemistry pharmacology administration & dosage MeSH
- Anti-Inflammatory Agents pharmacology administration & dosage chemistry MeSH
- Aspirin * administration & dosage pharmacology chemistry MeSH
- Prostaglandin-Endoperoxide Synthases metabolism MeSH
- Cyclooxygenase Inhibitors pharmacology administration & dosage chemistry MeSH
- Delayed-Action Preparations * MeSH
- Inflammation Mediators metabolism MeSH
- Mice MeSH
- Nanoparticles * chemistry MeSH
- Drug Carriers chemistry MeSH
- Polymers * chemistry administration & dosage MeSH
- Drug Liberation MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug (NSAID) commonly used in the treatment of pain, fever and inflammation. However, the administration of IBU in its free carboxylic acid form is strongly dependent on its limited solubility in aqueous solution. This mandates for an increased drug concentration to reach the therapeutic window, and promotes the alternative use of IBU sodium salt, even if this latter form poses significant constraints in terms of tunable release due to its uncontrolled and rapid diffusion. A potential solution is represented by oral administration through physical encapsulation of ibuprofen in designed carriers, despite this route limits the application of this therapeutic agent. In this work, we propose the covalent tethering of ibuprofen to a hydrogel matrix via esterification reaction. Exploiting the cleavability of the ester bond under physiological conditions, we propose a controlled drug delivery system where the whole drug payload can be released, thus overcoming the questioned aspects of over-dosage and solubility-dependent administration. In particular, we tested the biological activity of cleaved ibuprofen in terms of cyclooxygenase inhibition, reporting that chemical tethering did not alter the efficiency of the NSAID. Moreover, due to the sol-gel transition of the hydrogel matrix, these ibuprofen-functionalized hydrogels could be used as injectable tools in several clinical scenarios, performing a localized drug release and opening advanced avenues for in situ treatments.
- MeSH
- Acrylic Resins chemistry MeSH
- Administration, Oral MeSH
- Prostaglandin-Endoperoxide Synthases metabolism MeSH
- Enzyme Assays MeSH
- Hydrogels chemistry MeSH
- Ibuprofen administration & dosage pharmacokinetics MeSH
- Cyclooxygenase Inhibitors administration & dosage pharmacokinetics MeSH
- Delayed-Action Preparations administration & dosage pharmacokinetics MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Drug Carriers chemistry MeSH
- Propylene Glycols chemistry MeSH
- Solubility MeSH
- Sepharose chemistry MeSH
- Drug Liberation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Anti-Inflammatory Agents, Non-Steroidal pharmacokinetics classification adverse effects therapeutic use MeSH
- Ibuprofen * administration & dosage history pharmacokinetics adverse effects MeSH
- Cyclooxygenase Inhibitors administration & dosage history pharmacokinetics adverse effects MeSH
- Humans MeSH
- Drug-Related Side Effects and Adverse Reactions classification MeSH
- Arthritis, Rheumatoid * drug therapy MeSH
- Check Tag
- Humans MeSH
- Keywords
- magnesiumlaktát,
- MeSH
- Adrenergic beta-2 Receptor Agonists administration & dosage adverse effects therapeutic use MeSH
- Anti-Bacterial Agents administration & dosage adverse effects therapeutic use MeSH
- Calcium Channel Blockers administration & dosage adverse effects therapeutic use MeSH
- Cerclage, Cervical MeSH
- Glucocorticoids administration & dosage adverse effects therapeutic use MeSH
- Magnesium administration & dosage adverse effects therapeutic use MeSH
- Cyclooxygenase Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Lactates administration & dosage adverse effects therapeutic use MeSH
- Humans MeSH
- Oxytocin antagonists & inhibitors adverse effects therapeutic use MeSH
- Premature Birth * prevention & control MeSH
- Progestins administration & dosage adverse effects therapeutic use MeSH
- Magnesium Sulfate administration & dosage adverse effects therapeutic use MeSH
- Sympathomimetics administration & dosage adverse effects therapeutic use MeSH
- Pregnancy MeSH
- Tocolytic Agents * administration & dosage adverse effects therapeutic use MeSH
- Tocolysis methods MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Review MeSH
Non-steroidal anti-inflammatory drugs (NSAIDs) play an effective chemopreventive action against a variety of cancers. The present study aimed at targeting pro-inflammatory cyclooxygenase (COX) and NF-kB mediated inflammatory pathways in 9,10-dimethylbenzanthracene (DMBA) induced lung cancer in BALB/C mice and chemoprotective action of NSAIDs. Animals were divided into five groups and treated with NSAIDs, intratracheally, daily for a period of 18 weeks. Group 1 as control, received vehicle treatment; Group 2 received single dose of DMBA (10 mg/kg bw); Group 3, 4 and 5 besides DMBA treatment, also received Aspirin (60 mg/kg bw), Celecoxib (6.0 mg/kg bw) and Etoricoxib (0.6 mg/kg bw), respectively. DMBA induce DNA damage, apoptosis and expression of COX-1, COX-2 and NF-κB using immunofluorescence and blot analysis were done. The present study demonstrated the formation of micronuclei, over-expression of COX-2 and NF-κB in DMBA induced lung tumorigenesis and thereby suggesting a marked role of inflammation in the tumour progression. Results indicate the formation of micronuclei in DMBA group, which were significantly reduced in aspirin treated group, and totally absent in the celecoxib and etoricoxib groups. In conclusion, co-administration of etoricoxib and celecoxib has significantly reduced the inflammatory potential of the growing neoplasm in DMBA induced lung cancer in male BALB/C mice.
- MeSH
- Anthracenes administration & dosage pharmacology MeSH
- Anti-Inflammatory Agents, Non-Steroidal * administration & dosage pharmacology MeSH
- Chemoprevention MeSH
- DNA drug effects MeSH
- Cyclooxygenase Inhibitors administration & dosage pharmacology MeSH
- Disease Models, Animal MeSH
- Mice, Inbred BALB C MeSH
- Lung Neoplasms genetics immunology prevention & control MeSH
- Inflammation drug therapy immunology physiopathology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- magnesiumlaktát,
- MeSH
- Adrenergic beta-2 Receptor Agonists administration & dosage adverse effects therapeutic use MeSH
- Anti-Bacterial Agents administration & dosage adverse effects therapeutic use MeSH
- Calcium Channel Blockers administration & dosage adverse effects therapeutic use MeSH
- Cerclage, Cervical MeSH
- Glucocorticoids administration & dosage adverse effects therapeutic use MeSH
- Magnesium administration & dosage adverse effects therapeutic use MeSH
- Cyclooxygenase Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Lactates administration & dosage adverse effects therapeutic use MeSH
- Humans MeSH
- Oxytocin antagonists & inhibitors adverse effects therapeutic use MeSH
- Premature Birth * prevention & control MeSH
- Progestins administration & dosage adverse effects therapeutic use MeSH
- Magnesium Sulfate administration & dosage adverse effects therapeutic use MeSH
- Sympathomimetics administration & dosage adverse effects therapeutic use MeSH
- Pregnancy MeSH
- Tocolytic Agents * administration & dosage adverse effects therapeutic use MeSH
- Tocolysis methods MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Keywords
- Oxfordská liga analgetik, koanalgetika, adjuvantní analgetika,
- MeSH
- Substance Withdrawal Syndrome etiology prevention & control MeSH
- Algorithms MeSH
- Analgesics * administration & dosage adverse effects therapeutic use MeSH
- Antidepressive Agents therapeutic use MeSH
- Anti-Inflammatory Agents, Non-Steroidal administration & dosage adverse effects therapeutic use MeSH
- Antipyretics adverse effects therapeutic use MeSH
- Pain * drug therapy MeSH
- Chronic Disease drug therapy MeSH
- Cyclooxygenase 2 Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Cyclooxygenase Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Cannabinoids therapeutic use MeSH
- Humans MeSH
- Pain Management MeSH
- Drug-Related Side Effects and Adverse Reactions drug therapy MeSH
- Analgesics, Opioid * administration & dosage adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Practice Guideline MeSH
Trombocyty hrají významnou úlohu při hemostáze, a to účastí na mechanismu adheze, agregace, konstrikce, tvorbě trombu a hojení. Antiagregační přípravky působí proti funkci trombocytů, respektive proti primární hemostáze. Léky, které máme v současné době k dispozici, umožňují blokovat účinek krevních destiček na úrovni aktivace - jednak ireverzibilní acetylací cyklooxygenázy (COX-1), blokací reabsorpce adenosinu, inhibicí fosfodiesterázy 3 a inhibicí vazby ADP na destičkový receptor P2Y12. Jeden ze zásadních problémů antiagregační léčby vedle jejich nežádoucích účinků je rezistence na léčbu. Ta je také důvodem vývoje nových antiagregačních přípravků.
Platelets are important for hemostasis. Adhesion, aggregation, constriction, thrombus formation and healing as a mechanism of action. Antiplatelet drugs are drugs that counteract the platelet function, or against primary hemostasis. Drugs which are currently available allow to block the action of platelet activation level - firstly irreversible acetylation of cyclooxygenase (COX1), blocking reabsorption adenosine, inhibition of phosphodiesterase 3 and inhibition of binding of ADP to the P2Y12 platelet receptor. Resistance to treatment is one of the main problems antiplatelet therapy in addition to their adverse effects. What is the reason for the development of new antiplatelet drugs.
- Keywords
- CLOPIDOGREL, prasugrel, elinogrel, cangrelor,
- MeSH
- Purinergic P2Y Receptor Antagonists pharmacology therapeutic use MeSH
- Purinergic P2 Receptor Antagonists pharmacology therapeutic use MeSH
- Aspirin administration & dosage pharmacology therapeutic use MeSH
- Stroke prevention & control MeSH
- Drug Resistance, Neoplasm MeSH
- Dipyridamole pharmacology therapeutic use MeSH
- Platelet Aggregation Inhibitors * pharmacology therapeutic use MeSH
- Cyclooxygenase Inhibitors administration & dosage pharmacology therapeutic use MeSH
- Phosphodiesterase 3 Inhibitors pharmacology therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Ticagrelor MeSH
- Ticlopidine pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Keywords
- Veral,
- MeSH
- Acute Pain drug therapy MeSH
- Analgesics administration & dosage adverse effects therapeutic use MeSH
- Anti-Inflammatory Agents, Non-Steroidal administration & dosage adverse effects therapeutic use MeSH
- Chronic Pain drug therapy MeSH
- Diclofenac * pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Cyclooxygenase Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Dosage Forms MeSH
- Humans MeSH
- Pain Management * MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Drug Administration Schedule MeSH
- Check Tag
- Humans MeSH
Léčba osteoartrózy musí být komplexní a zahrnovat přístupy nefarmakologické, farmakologické i chirurgické. Přehledová práce se věnuje možnostem farmakoterapie. Existují poměrně rozsáhlá klinická data ukazující na symptomy modifikující účinek nesteroidních antirevmatik, paracetamolu, opioidů, intraartikulárně aplikovaných kortikosteroidů, ale také přípravků označovaných jako SYSADOA (symptomatic slow acting drug in OA), mezi které se řadí chondroitin sulfát, glukosamin sulfát, diacerein, ASU (Piascledinee) či kyselina hyaluronová. Ačkoliv některé přípravky disponují údaji o zpomalení radiografické progrese, strukturu modifikující účinek léků ze skupiny SYSADOA není všeobecně přijímán. V současnosti probíhá řada klinických studií s novými kandidátními molekulami. Otázka, zda lze v blízké budoucnosti očekávat nástup éry chorobu modifikujících léků (DMOAD – disease modifying osteoarthritis drug), však zůstává stále otevřená.
The treatment of osteoarthritis should be comprehensive and include non-pharmacological, pharmacological as well as surgical approaches. The present overview summarizes the possibilities of pharmacotherapy. Relatively extensive clinical data have been accumulated that point to the symptom-modifying effect of non-steroid antirheumatic drugs, acetaminophen (paracetamol), opioids, intra-articular corticosteroids, but also preparations referred to as SYSADOAs (symptomatic slow acting drugs in OA) that include chondroitin sulphate, glucosamine sulphate, diacerein, ASU (Piascledine), or hyaluronic acid. Though some preparations rely on data showing reduced rate of radiological progression, the structure-modifying effects of the drugs from the SYSADOA group have not obtained general acceptance. A number of clinical studies testing new candidate molecules are currently underway. No answer has been provided yet to the question whether we can anticipate the advent of an era of disease modifying osteoarthritis drugs (DMOADs) in the near future.
- MeSH
- Anthraquinones adverse effects therapeutic use MeSH
- Anti-Inflammatory Agents, Non-Steroidal * administration & dosage adverse effects MeSH
- Antirheumatic Agents * administration & dosage adverse effects MeSH
- Chondroitin Sulfates pharmacology therapeutic use MeSH
- Drug Combinations MeSH
- Phytosterols therapeutic use MeSH
- Adrenal Cortex Hormones pharmacology therapeutic use MeSH
- Cyclooxygenase Inhibitors administration & dosage pharmacology adverse effects MeSH
- Injections, Intra-Articular methods MeSH
- Hyaluronic Acid administration & dosage MeSH
- Humans MeSH
- Analgesics, Opioid pharmacology adverse effects therapeutic use MeSH
- Organometallic Compounds therapeutic use MeSH
- Osteoarthritis * diagnosis drug therapy classification MeSH
- Plant Extracts therapeutic use MeSH
- Drug Administration Schedule MeSH
- Thiophenes therapeutic use MeSH
- Vitamin E MeSH
- Check Tag
- Humans MeSH
