The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres

The aim of the present study was to prepare valdecoxib, a cyclo-oxygenase-2 enzyme inhibitor, as a loaded multiparticulate system to achieve site-specific drug delivery to colorectal tumors. Film coating was done with the pH-sensitive polymer Eudragit S100 and sodium alginate was used as mucoadhesive polymer in the core. The microspheres were characterized by X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy and were evaluated for particle size, drug load, in vitro drug release, release kinetics, accelerated stability, and extent of mucoadhesion. The coated microspheres released the drug at pH 7.4, the putative parameter for colonic delivery. When applied to the mucosal surface of freshly excised goat colon, microspheres pretreated with phosphate buffer pH 7.4 for 30 minutes showed mucoadhesion. To ascertain the effect of valdecoxib on the viability of Caco-2 cells, the 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide) test was conducted using both valdecoxib and coated microspheres. In both cases, the percentage of dehydrogenase activity indicated a lack of toxicity against Caco-2 cells in the tested concentration range. Drug transport studies of the drug as well as the coated microspheres in buffers of pH 6 and 7.4 across Caco-2 cell monolayers were conducted. The microspheres were found to exhibit slower and delayed drug release and lower intracellular concentration of valdecoxib

Biological activities of <i style="">Ocimum sanctum</i> L. fixed oil—An overview

403-412Seeds of Ocimum sanctum L. (Labiatae; popularly known as ‘Tulsi’ in Hindi and ‘Holy Basil’ in English) contain a pale yellow colored fixed oil. The oil possesses antiinflammatory activity due to dual inhibition of arachidonate metabolism supplemented by antihistaminic activity. The antiinflammatory activity is not dependent on the pituitary adrenal axis. The oil possesses antipyretic activity due to prostaglandin inhibition and peripherally acting analgesic activity. The oil has been found to be effective against formaldehyde or adjuvant induced arthritis and turpentine oil induced joint edema in animals. Lipoxygenase inhibitory histamine antagonistic and antisecretory activities of the oil contribute towards antiulcer activity. The oil can inhibit enhancement of vascular capillary permeability and leucocyte migration following inflammatory stimulus. The LD50 of the oil is 42.5 ml/kg and long-term use of oil at 3 ml/kg dose does not produce any untoward effects in rats. The oil contains -linolenic acid, an ω-3 fatty acid which on metabolism produces eicosapentaenoic acid and the same appears to be responsible for the biological activity. The oil has hypotensive anticoagulant and immunomodulatory activities. Antioxidant property of the oil renders metabolic inhibition, chemoprevention and hypolipidaemic activity. Presence of linolenic acid in the oil imparts antibacterial activity against Staphylococcus aureus. The oil alone or in combination with cloxacillin a β-lactamase resistant penicillin has been found to be beneficial in bovine mastitis an inflammatory disorder resulting from staphylococcal infection. Existence of anti-inflammatory analgesic and antibacterial activities in single entity i. e.fixed oil appears to be unique

Effect of formulation factors on in vitro transcorneal permeation of voriconazole from aqueous drops

The purpose of this research was to evaluate the effect the formulation factors on in vitro permeation of voriconazole through freshly isolated goat and sheep corneas. An increase in the pH of the drops from 4.0 to 8.0 resulted in significant (P < 0.05) increase drug permeation. Raising concentration of the drops from 0.05% to 0.2% (w/v) significantly, (P < 0.05) increased drug permeation, but decreased the percent permeation. Corneal transport of voriconazole is both pH and concentration dependent. Eye drops containing disodium edetate (ethylenediaminetetraacetic acid) alone or combination with benzalkonium chloride showed significantly (P < 0.05) higher permeation as compared with control formulation. Addition of beta-cyclodextrin to the formulation enhanced corneal permeation of voriconazole. Compared with control formulation, voriconazole 0.2% (w/v) drop containing viscosity modifier produced significant (P < 0.05) decrease in permeation. Most of the formulations showed higher zone of inhibition against Candida albicans

Antiinflammatory, analgesic and antipyretic activities of <i style="">Linum usitatissimum</i> L. (flaxseed/linseed) fixed oil

932-938The fixed oil of L. usitatissimum (flaxseed/linseed) inhibited PGE2-, leukotriene-, histamine- and bradykinin-induced inflammation. The oil also inhibited arachidonic acid-induced inflammation, suggesting its capacity to inhibit both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism. In tail immersion model, the oil raised the pain threshold to a lesser extent than morphine but showed excellent peripherally acting, analgesic activity comparable to aspirin, against acetic acid-induced writhing in mouse. In typhoid paratyphoid A/B vaccine-induced pyrexia, the oil showed antipyretic activity comparable to aspirin. The oil contains 57.38% -linolenic acid. Dual inhibition of arachidonic acid metabolism, antihistaminic and antibradykinin activities of the oil could account for the biological activity and the active principle could be -linolenic acid an omega-3 (18:3, n-3) fatty acid. </span

Generation of ceramide in murine macrophages infected with Leishmania donovani alters macrophage signaling events and aids intracellular parasitic survival

In the present study, we examined the involvement of intracellular ceramide in host pathogen interaction of BALB/c mouse peritoneal macrophages infected with the obligate intracellular protozoan, Leishmania donovani. Our findings indicate that the level of intracellular ceramide was enhanced as a result of the in vitro infection. While the elevated ceramide was largely due to de novo synthesis, activation of the sphingomyelinases was also observed. The enhanced ceramide was responsible for the downregulation of classical PKC activity, upregulation of calcium independent atypical PKC-ζ expression and activity of calcium independent PKC. Ceramide also impaired the phosphorylation of MAPK. Evidently, ceramide suppressed the generation of nitric oxide during leishmanial infection and also facilitated the survival of leishmanial parasites in the intramacrophageal milieu. These data present newer insight to the signaling events in leishmania-infected murine macrophages, which might offer ceramide as a new therapeutic target in the future. (Mol Cell Biochem 223: 47–60, 2001