Effect of liposomal celecoxib on proliferation of colon cancer cell and inhibition of DMBA-induced tumor in rat model

Celecoxib, a selective cyclooxygenase-2 inhibitor, has shown potential anticancerous activity against majority of solid tumors especially on patients with colon cancer. However, associations of serious side effects limit the usage of celecoxib in colon cancer treatment. To address this issue and provide an alternative strategy to increase the efficacy of celecoxib, liposomal formulation of celecoxib was prepared and characterized. Anticancer activity of liposomal celecoxib on colon cancer cell HCT 15 was evaluated in vitro. Furthermore, tumor inhibition efficiency by liposomal celecoxib was studied on 7,12-dimethyl benz(a)anthracene (DMBA)-induced tumor in rat model. In order to elucidate the antioxidant activity of celecoxib-loaded liposomes, antioxidant superoxide dismutase (SOD) generation and lipid peroxide (LPx) formation in both liver and kidney tissues were examined. Characterization of the formed unilamellar liposomes revealed the formation of homogeneous suspension of neutral (empty) or anionic (celecoxib-loaded) liposomes with a well-defined spherical shape which have a mean size of 103.5 nm (empty liposome) and 169 nm (liposomal celecoxib). High-performance liquid chromatography (HPLC) analysis and hemolytic assay demonstrated 46% of celecoxib entrapment efficiency and significantly low hemolysis, respectively. Liposomal celecoxib exhibited dose-dependent cytotoxicity and apoptotic activity against HCT 15 cells which are comparable to free celecoxib. In vivo study demonstrated inhibition of tumor growth. Biochemical analysis of the liposomal celecoxib-treated group significantly inhibited the LPx formation (oxygen-free radicals) and increased the activity of SOD. Our results present the potential of inhibiting colon cancer in vitro and DMBA-induced tumor in rat model in vivo by liposomal celecoxib

Human serum albumin nanoparticles loaded with phthalocyanine dyes for potential use in photodynamic therapy of atherosclerotic plaques

Diseases caused by obstruction or rupture of vulnerable plaques in the arterial walls such as cardiovascular infarction or stroke are the leading cause of death in the world. In the present work, we developed human serum albuminnanoparticles loaded by physisorption with zinc phthalocyanine, TT1, mainly used for industrial application as near-infrared photosensitizer and compared these to HSA NPsloaded with the well-known silicone phthalocyanine (Pc4). The use of NIR light allows for better tissue penetration, while the use of nanoparticles permitshigh local concentrations. The particles were characterized and tested for toxicity and stability as well as for their potential use as a contrast agent and NIR photosensitizer for photodynamic therapy in cardiovascular disease. We focused on the distribution of the nanoparticles in RAW264.7macrophage cells and atherosclerotic mice. The nanoparticles had an average size of 120 nm according todynamic light scattering, good loading capacity for zinc phthalocyanine,and satisfying stability in 50% (v/v) fetal bovine serum for 8 hours and in an aqueous environment at 4°C for 4–6 weeks. Under light irradiation we found a high production of singlet oxygen and the products showed no dark toxicity in vitro with macrophages(the target cells in vulnerable plaques),but at a low μg/mL nanoparticleconcentration killed efficiently the macrophagesupon LED illumination. Injection of the contrast agentin atherosclerotic mice led to a visible fluorescence signal of zinc phthalocyaninein the atherosclerotic plaque at 30 minutes and in the lungs with afast clearance of the nanoparticles. Zinc phthalocyanine loaded human serum albumin nanoparticles present an interesting candidate for the visualization and potentially photodynamictreatment of macrophages in atherosclerotic plaquesThe research leading to these results has received funding from FP7-NMP CosmoPHOS-Nano under grant agreement No. 310337. Additional funding was received by the Spanish groups from MINECO (CTQ2017-85393-P) and ERA-NET/MINECO EuroNanoMed2017-191 / PCIN-2017-04

Appraisal of trawl fisheries of India with special reference on the changing trends in bycatch utilization

Trawl fisheries sector account more than 50% of the marine fisheries production of India. Annual average fish landing from trawlers was 17, 21, 000 t (2008-2011), which formed around 51 % of the marine fish landing of the coast. In this about 51% of the catch was contributed by the west coast and remaining by the east coast of India. Recent studies of the trawl fishery in India have shown that incidental catches/low value bycatch (LVB) landing and utilization has increased over the period of time. The present study is based on the data collected from major trawl landing centres along the coast of India during the period 2008-2011.The estimated landing of low value bycatch (LVB) in trawl fisheries, increased from 14 % in 2008 to 25 % in 2011, which is reflected as reduction in discard volume by trawlers. On an average the highest quantity of LVB landed was in Veraval (50,000 t) and in Mangalore, LVB landing increased from 3% in (3000 t) in 2008 to 26 % (12,000 t) in 2011.In Mumbai, the percentage of trash fish landed remained around 5% during the study period. In Calicut, the LVB landed in 2011 contributed 26% to the total landings by the trawl. In Kochi, Kerala the total LVB landed in 2011 was 1,992 t forming 7.2 % of the total landing. In Chennai, Tamilnadu, the LVB landing which was 13 % in 2008 increased to 17% in 2011, while in Visakhapatanam, Andhra Pradesh, LVB landing showed a steady increase from 2% in 2008 to 21% in 2011. The landing centre price for LVB showed an increasing trend due to increased demand for trash fish for the production of fish meal and fertilizer. The dominance of finfishes in LVB found to increase the value of LVB and the value realized for 30,000 t of LVB in Available online at: www.mbai.org.in doi: 10.6024/jmbai.2013.55.2.01765-11 Mangalore in 2011 ( Rs.280 million) was more than that realized for 50,000 t of LVB in Veraval (Rs.200 million). A disturbing trend observed from the studies in Mangalore was that, the sardines in trash fetches higher price in some seasons (upto Rs.16/kg) compared to a lower price when landed in fresh form, and the percentage of sardines in LVB is found to be very high (24% in 2010). This trend may cause a severe threat to the protein availability to the rural poor. Looking at the trend of trawl landing during 2008-2012, it is seen that even though the trawl landing showed an increase over the period of time, the edible portion of the trawl landing did not show any significant increase rather showing general declining trend. Study on the bycatch from different centres along the coast of India showed that as many as 237 species / groups of marine fauna with juveniles of commercially important fishes were landed as LVB. Increase in utilization of LVB (which was discarded earlier) from trawl fishery, a trend which is market driven and its implication on the ecosystem and marine fisheries production of the country is discussed in this paper

Probing the potential of apigenin liposomes in enhancing bacterial membrane perturbation and integrity loss

Along with discovery of new antibacterial agents, it is important to develop novel drug delivery systems to effectively deliver drugs within bacterial cells for enhanced therapeutic activity. Liposomes have been extensively investigated as pharmaceutical carriers for improvement of therapeutic index of antimicrobial agents. The aim of this present study was to evaluate the antibacterial activity of free and liposomal formulation of apigenin, a plant based isoflavone and elucidate the mode of action. Distearoylphosphatidylcholine liposomes were prepared having nano-range particle size (104.3 ± 1.8 nm), narrow particle distribution (0.204) and high encapsulation efficiency of apigenin (89.9 ± 2.31%). Antibacterial activity of apigenin and efficacy of liposome-mediated apigenin delivery were determined from minimum inhibitory concentration values. Interaction studies using electron microscopy revealed adherence and fusion of liposomal apigenin with the bacteria causing membrane perturbation through reactive oxygen species generation which was evaluated by epi-fluorescence microscopy and fluorescence activated cell sorting. The interaction of apigenin liposomes with bacterial membrane increased intracellular drug concentration and thus, can be employed to deliver apigenin within cells to augment its antibacterial activity. Increased efficacy and hemocompatibility of this formulation paves way for future evaluation of underlying molecular mechanisms and in vivo testing for enhanced therapeutic effects

Reversal of Warburg effect by Apigenin and 5-Fluorouracil loaded dual drug liposomes result in enhanced colorectal chemotherapy

Recent combinatorial approaches have demonstrated multidrug-based chemotherapy which target multiple pathways simultaneously leading to enhanced efficacy and reduced toxicity. Our study reports simultaneous delivery of 5-Fluorouracil (a clinically approved drug) and Apigenin (a naturally occurring isoflavonoid abundantly present in fruit and vegetables) through a single liposome to combat and control colon cancer effectively in-vitro and in-vivo based on synergy studies after screening natural product library. Uniform homogeneous suspension of dual drug-loaded large unilamellar vesicles with substantial entrapment of both drugs was obtained by modified thin film hydration method. The vesicles exhibited excellent hemocompatibility and cytocompatibility against normal fibroblasts. The cytotoxicity and cellular effects of individual and combinatorial free drugs, neat vesicles and single or dual drug-loaded liposomes tested against different human colon cancer cell lines revealed significantly higher cytotoxicity of dual-drug liposomes in comparison to other formulations. The dual drug loaded liposomal formulation was observed to be effectively internalized by endocytosis and demonstrated enhanced inhibition of angiogenesis, better reduction in cell proliferation, increased apoptotic potential and significantly decreased cellular migration and invasion capacity. Cell signaling studies indicating a significant upregulation of AMPK and activity against downstream targets by dual drug liposomes resulted in apoptosis, autophagy and senescence, suggesting its role in the reversal of Warburg effect. Enhanced apoptotic potential of the formulation was traced to its ability to induce greater oxidative stress through the generation of reactive oxygen and nitrogen species. The formulation was tested in a preclinical setting in nude mice tumor xenograft model and was found to have greater anti-neoplastic and anti-tumorigenic effect. The study indicated the potential of the synergistic effect of Apigenin in 5-Fluorouracil treatment of colon cancer which effectively circumvents the problem of drug resistance and 5-Fluorouracil associated toxicity. This dual drug loaded liposomal formulation thus, offers a new attractive alternative to enhance the therapeutic potency of drugs and paves way for potential clinical applications

Not Available

Not AvailableTrawl fisheries sector account more than 50% of the marine fisheries production of India. Annual average fish landing from trawlers was 17, 21, 000 t (2008-2011), which formed around 51 % of the marine fish landing of the coast. In this about 51% of the catch was contributed by the west coast and remaining by the east coast of India. Recent studies of the trawl fishery in India have shown that incidental catches/low value bycatch (LVB) landing and utilization has increased over the period of time. The present study is based on the data collected from major trawl landing centres along the coast of India during the period 2008-2011.The estimated landing of low value bycatch (LVB) in trawl fisheries, increased from 14 % in 2008 to 25 % in 2011, which is reflected as reduction in discard volume by trawlers. On an average the highest quantity of LVB landed was in Veraval (50,000 t) and in Mangalore, LVB landing increased from 3% in (3000 t) in 2008 to 26 % (12,000 t) in 2011.In Mumbai, the percentage of trash fish landed remained around 5% during the study period. In Calicut, the LVB landed in 2011 contributed 26% to the total landings by the trawl. In Kochi, Kerala the total LVB landed in 2011 was 1,992 t forming 7.2 % of the total landing. In Chennai, Tamilnadu, the LVB landing which was 13 % in 2008 increased to 17% in 2011, while in Visakhapatanam, Andhra Pradesh, LVB landing showed a steady increase from 2% in 2008 to 21% in 2011. The landing centre price for LVB showed an increasing trend due to increased demand for trash fish for the production of fish meal and fertilizer. The dominance of finfishes in LVB found to increase the value of LVB and the value realized for 30,000 t of LVB in Available online at: www.mbai.org.in doi: 10.6024/jmbai.2013.55.2.01765-11 Mangalore in 2011 ( Rs.280 million) was more than that realized for 50,000 t of LVB in Veraval (Rs.200 million). A disturbing trend observed from the studies in Mangalore was that, the sardines in trash fetches higher price in some seasons (upto Rs.16/kg) compared to a lower price when landed in fresh form, and the percentage of sardines in LVB is found to be very high (24% in 2010). This trend may cause a severe threat to the protein availability to the rural poor. Looking at the trend of trawl landing during 2008-2012, it is seen that even though the trawl landing showed an increase over the period of time, the edible portion of the trawl landing did not show any significant increase rather showing general declining trend. Study on the bycatch from different centres along the coast of India showed that as many as 237 species / groups of marine fauna with juveniles of commercially important fishes were landed as LVB. Increase in utilization of LVB (which was discarded earlier) from trawl fishery, a trend which is market driven and its implication on the ecosystem and marine fisheries production of the country is discussed in this paper.Not Availabl