Abstract. The purpose of the study was to prepare and evaluate the anti-inflammatory activity of cyclodextrin (CD) complex of curcumin for the treatment of inflammatory bowel disease (IBD) in colitisinduced rat model. Inclusion complexes of curcumin were prepared by common solvent and kneading methods. These complexes were further evaluated for increase in solubility of poorly soluble curcumin. The inclusion complexes were characterized for enhancement in solubility, in vitro dissolution, surface morphology, infrared, differential scanning calorimetry, and X-ray studies. Solubility, phase solubility, and in vitro dissolution studies showed that curcumin has higher affinity for hydroxypropyl-β-CD (HPβCD) than other CDs. HPβCD complex of curcumin was further investigated for its antiangiogenic and anti-inflammatory activity using chick embryo and rat colitis model. HPβCD complex of curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in chorioallantoic membrane assay. Curcumin-and HPβCD-treated rats showed a faster weight gain compared to dextran sulfate solution (DSS) controls. Whole colon length appeared to be significantly longer in HPβCD-treated rats than pure curcumin and DSS controls. An additional finding in the DSStreated rats was the predominance of eosinophils in the chronic cell infiltrate. Decreased mast cell numbers in the mucosa of the colon of CD of curcumin-and pure-curcumin-treated rats was observed. This study concluded that the degree of colitis caused by administration of DSS was significantly attenuated by CD of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for IBD patients.

Background:Lung administration of antibiotics by nebulization is promising for improved treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, lipid particulate system may improve lung delivery.Materials and Methods:We investigated rifampicin-loaded freeze-dried liposomes. Various formulations were prepared with different drug lipid ratios and one formulation was optimized. Optimized colloidal liposome formulation was freeze-dried and subsequently subjected for various evaluation and characterization parameters such as in-vitro dissolution, in-vitro antitubercular activity, aerodynamic characters, surface morphology, and thermal behavior. The optimized formulation of rifampicin-loaded freeze-dried liposome and free rifampicin was subjected for the in-vivo drug disposition study in Wister rat model by intra-tracheal instillation in comparison with an oral route of administration.Results:The results of pharmacokinetic study for both free drug and the formulation suggested that liposomes released the drug in a controlled manner for a longer period of time. The enhanced efficiency of drug incorporated into liposomes suggested that the delivery of encapsulated drugs to macrophages was more rapid than that of free drug.Conclusion:Therefore, the pharmacokinetic and drug disposition studies provided a sound basis for predicting the successful treatment for tuberculosis.

The aim of this study was to prepare tamoxifen citrate loaded cylindrical polymeric implants for application at tumor sites. The implant was based on poly (sebacic acid-co-ricinoleic-ester anhydride) 70 : 30 w/w [poly(SA-RA) 70 : 30 w/w], a low-melting, biodegradable, and biocompatible polymer. Implants were prepared by a standardized melt manufacturing method. Differential scanning calorimetry and scanning electron microscopy were used for implant characterization. In vitro drug release studies were performed in phosphate-buffered saline (pH 7.4) at 37 6 28C. The drug content was estimated by high-performance liquid chromatography. The differential scanning calorimetry studies showed that the tamoxifen citrate in the implants was in the amorphous state. The cumulative percentage of drug release from 10 and 20 wt % drug-loaded poly(SA-RA) 70 : 30 w/w implants after 30 days was found to be 42.36 and 62.60%, respectively.

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Pioglitazone, a class II Biopharmaceutical Classification System drug having poor water solubility and slow dissolution rate may have a negative impact on its subtherapeutic plasma drug levels leading to therapeutic failure. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The phase solubility studies were carried using three different types of cyclodextrins viz., β, methyl-β and γ-cyclodextrins. The Gibbs free energy was calculated in order to determine ease of the complexation. Binary systems of pioglitazone with cyclodextrins were prepared by kneading method and spray drying method. The phase solubility profiles with all the three cyclodextrins were classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complexes. The complexation capability of cyclodextrins with pioglitazone increased in the order of methyl-β > β > γ-cyclodextrin. The Gibbs free energy was found to be in the order γ > methyl-β > β cyclodextrin. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, Fourier transformation-infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry studies. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Greater solubility was observed with spray-dried methyl-β cyclodextrin complexes (2.29 ± 0.001 mg/ml) in comparison to the kneaded methyl-β cyclodextrin complexes (1.584 ± 0.053 mg/ml) and pure drug (0.0714 ± 0.0018 mg/ml).

The degree of colitis caused by administration of DSS was significantly attenuated by colonic delivery of SLMs of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for inflammatory bowel disease patients.

Objective:To evaluate the protective effect of glibenclamide against the experimental diabetes-induced nuclear damage in Wistar rats.Materials and Methods:The anti-mutagenic effect of glibenclamide (0.5, 5 and 50 mg/kg, p.o daily for 4 weeks) was evaluated against the nicotinamide (NA)-streptozotocin (STZ) induced type-2 diabetes mellitus using bone marrow micronucleus and sperm abnormalities tests. The antioxidant status was tested by estimating the serum levels of lipid peroxidation (LPO), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx).Results:The results indicated that glibenclamide at 50 mg/kg decreased the frequency of micronuclei in erythrocytes (P < 0.05) and sperm shape abnormality (P < 0.01) besides enhancing the antioxidant status (P < 0.05) in the diabetic rats. However, glibenclamide treatment did not enhance the polychromatic and normochromatic erythrocytes (P/N) ratio and sperm count in the diabetic condition.Conclusion:The observations indicate that the glibenclamide has anti-mutagenic potential which could be related to the antioxidant effect and might also possess anti-proliferative property.

Metformin hydrochloride (MH), a biguanide antidiabetic, is the drug of choice in obese patients. It is well absorbed from the upper part of gastrointestinal tract and has oral bioavailability of 50% to 60%. The objective of this study was to formulate MH into floating microspheres in order to increase its residence time at the site of absorption and thus improve its bioavailability; and to extend the duration of action along with possibilities of dose reduction. Microspheres were prepared by emulsion solvent evaporation method and evaluated for particle size, entrapment efficiency, buoyancy, and in vitro release; and further characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The pharmacokinetic and pharmacodynamic evaluation of selected formulation was carried out in male Wistar diabetic rats. The data was statistically analyzed by unpaired t-test. A 3.5-fold increase in relative bioavailability was observed. The prolongation of half-life (t(1/2)) from 4.5 ± 2.41 h to 14.12 ± 4.81 h indicated extended duration of action. Oral glucose tolerance test (OGTT) was analyzed by one-way analysis of variance followed by Dunnet multiple comparison test, a significant decrease (p < 0.05) in the blood glucose levels was observed when formulations were compared with control rats. Hence, MH floating microspheres were tested at 50 mg/kg and 100 mg/kg body weight, OGTT data showed nonsignificant difference (p >0.05). In conclusion, an effective oral antidiabetics treatment can be achieved by formulating MH into floating microspheres which results in increase in bioavailability along with extended duration of action resulting in possible reduction in dose.