Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 10, Issue 5, 2011

Over recent years, non-steroidal anti-inflammatory drugs (NSAIDs) have been increasingly introduced as topical preparations as they are simple to apply and deliver high drug concentrations locally with limited side effects. Ketorolac trometamol (KT), a potent COX-2 inhibitor, produces typical side effects of NSAIDs when given orally and systemically. Hence the present investigation encompasses the development of topical formulations employing different dermatological bases and evaluated for its efficacy and safety. Standard procedures were followed to test the antiinflammatory and antihyperalgesic effects in male Wistar albino rats. Amongst the various semisolid formulations, the formulation containing hydroalcoholic carbopol gel base (KT1) was found to be significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation (79.69±1.51 after 5 h of carrageenan administration) as compared to formulation containing plain carbopol gel base (68.75±2.76) and PEG base 73.44±1.23. This demonstrates the suitability of carbopol gel base as an ideal dermatological base for ketorolac trometamol topical formulation and thus providing an ample credence for better therapeutic efficacy.

Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes doublestranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections.

Naproxen is a propionic acid derivative related to the arylacetic acid group. This drug is one of the most popular non-steroidal anti-inflammatory agents. It is a non-selective cyclooxygenase inhibitor and is advocated for use in painful and inflammatory rheumatic and non-rheumatic conditions. In low risk patients, naproxen and ibuprofen may be the first choice agents because they are effective, well tolerated and inexpensive. Naproxen is rapidly and completely absorbed from the gastrointestinal tract with an in vivo bioavailability of 95% and elimination half-life is 12 to 17 h. It has a volume of distribution of 0.16 L/Kg and at therapeutic levels, it is more than 99% albumin-bound. Although introduced long back, several efforts have been done to develop its prodrugs and analytical procedures. The current article describes chemistry, pharmacology, pharmacokinetics, adverse effects, interactions and contraindications of naproxen. A special emphasis is laid on the review of recent literature of various prodrugs synthesized and analytical methods developed for determination of naproxen in pharmaceutical preparations.

Chronic inflammation has been identified as a significant factor in the carcinogenesis of various tumors, including pancreatic cancer. Both hereditary and classical forms of chronic pancreatitis are associated with an increased risk of developing pancreatic cancer. Cytokines and other mediators of the inflammatory process together with an upregulation of pro-inflammatory pathways play a pivotal role in oncogenesis' stimulation, tumor growth and metastasis. The presence of a strong desmoplastic reaction within and around pancreatic cancer cells renders the proteolytic degradation of extracellular matrix components an essential process for tumor invasion and metastasis. Various classes of proteases produced by the pancreatic acinar cells are involved in these proteolytic events. The multiple link between inflammation and pancreatic cancer may represent the basis for a novel antineoplastic strategy. Cytokines, proteases, reactive-oxygen-species, cyclooxygenase-2, nuclear-factor-κB and perixosome proliferator-activated receptor-γ may be a new molecular targets useful for therapeutic purpose.