Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide, is a specific cyclooxygenase-2 (COX-2) inhibitor with no inhibition of cyclooxygenase-1 at therapeutic doses. It is being used successfully for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, familial adenomatous polyposis and primary dysmenorrhea. 1,2) Celecoxib also demonstrated significant chemopreventive activity in colon carcinogenesis, ultraviolet B radiation (UVB) induced skin cancer and breast cancer. [3][4][5] Celecoxib is weakly acidic (pK a is 11.1) and hydrophobic (Log P is 3.5) and its low aqueous solubility (3-7 mg/ml) contributes to high variability in absorption after oral administration. 6)The molecule exists in three polymorphic forms and its solid-state interconversion between the forms at ordinary temperatures has not been observed. It is isolated as agglomerates of long needle-shaped crystals, which exhibit cohesiveness, low bulk density and compressibility, and poor flow properties that impart complications in it's processing into solid dosage forms.7) According to biopharmaceutical classification system, celecoxib is classified as a low solubility and high permeability drug. 6) Therefore, the particle size of celecoxib influences the content uniformity, dissolution and bioavailability of the product. The t max of celecoxib is about three hours after oral administration. Rapid onset of action is necessary to provide fast pain relief in the treatment of acute pain. Therefore, it is necessary to enhance the aqueous solubility and dissolution rate of celecoxib to obtain faster onset of action, to minimize the variability in absorption and improve its overall oral bioavailability. This can be achieved by formulating the drug in lipid-based systems.Among the lipid-based systems, self-microemulsifying drug delivery system (SMEDDS) is a promising technology to improve the rate and extent of the absorption of poorly water-soluble drugs. [8][9][10][11][12][13][14][15] The clinical usefulness of the SMEDDS is evident from the commercially available formulations containing cyclosporin A, ritonavir and Saquinavir. 16,17) SMEDDS are comprised of mixture of drug, oil, surfactant(s) and/or co-solvents which form fine oil in water and/or water in oil microemulsions upon dilution with aqueous medium or in vivo administration. SMEDDS enhances the bioavailability of poorly water-soluble drugs through solubilization in the excipient matrix or interface and dispersion in the gastrointestinal tract. Relatively small size of the dispersed oil droplets in nanometer range and very high surface area to volume ratio are advantages of the microemulsion. These characteristics result in faster drug release from microemulsion in a reproducible manner, which can be designed further to make the release characteristics independent of the gastro intestinal physiology and the fed/fasted state of the patient. 8,[18][19][20] In this study, we have developed an optimized formulation using a self-microemulsifying system in...

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and an irreversible lung disorder characterized by the accumulation of fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be one of the possible sources for a substantial increase in the number of fibroblasts/myofibroblasts in IPF lungs. Tannic acid (TA), a natural dietary polyphenolic compound has been shown to possess diverse pharmacological effects. However, whether TA can inhibit TGF-β1-mediated EMT in lung epithelial cells remains enigmatic. Both the human adenocarcinomic alveolar epithelial (A549) and normal bronchial epithelial (BEAS-2B) cells were treated with TGF-β1 with or without TA. Results showed that TA addition, markedly inhibited TGF-β1-induced EMT as assessed by reduced expression of N-cadherin, type-1-collagen, fibronectin, and vimentin. Furthermore, TA inhibited TGF-β1-induced cell proliferation through inducing cell cycle arrest at G0/G1 phase. TGF-β1-induced increase in the phosphorylation of Smad (Smad2 and 3), Akt as well as that of mitogen activated protein kinase (ERK1/2, JNK1/2, and p38) mediators was effectively inhibited by TA. On the other hand, TA reduced the TGF-β1-induced increase in TGF-β receptors expression. Using molecular docking approach, FTIR, HPLC and Western blot analyses, we further identified the direct binding of TA to TGF-β1. Finally, we conclude that TA might directly interact with TGF-β1, thereby repressing TGF-β signaling and subsequent EMT process in lung epithelial cells. Further animal studies are needed to clarify its potential therapeutic benefit in pulmonary fibrosis.

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A B S T R A C TRheumatoid arthritis (RA) is the most common complex multifactorial joint related autoimmune inflammatory disease with unknown etiology accomplished with increased cardiovascular risks. RA is characterized by the clinical findings of synovial inflammation, autoantibody production, and cartilage/bone destruction, cardiovascular, pulmonary and skeletal disorders. Pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and IL-10 were responsible for the induction of inflammation in RA patients. Drawbacks such as poor efficacy, higher doses, frequent administration, low responsiveness, and higher cost and serious side effects were associated with the conventional dosage forms for RA treatment. Nanomedicines were recently gaining more interest towards the treatment of RA, and researchers were also focusing towards the development of various anti-inflammatory drug loaded nanoformulations with an aid to both actively/passively targeting the inflamed site to afford an effective treatment regimen for RA. Alterations in the surface area and nanoscale size of the nanoformulations elicit beneficial physical and chemical properties for better pharmacological activities. These drug loaded nanoformulations may enhances the solubility of poorly water soluble drugs, improves the bioavailability, affords targetability and may improve the therapeutic activity. In this regimen, the present review focus towards the novel nanoparticulate formulations (nanoparticles, nanoemulsions, solid lipid nanoparticles, nanomicelles, and nanocapsules) utilized for the treatment of RA. The recent advancements such as siRNA, peptide and targeted based nanoparticulate systems for RA treatment were also discussed. Special emphasis was provided regarding the pathophysiology, prevalence and symptoms towards the development of RA.