Oral probiotic microcapsule formulation ameliorates non-alcoholic fatty liver disease in Bio F1B Golden Syrian hamsters.

The beneficial effect of a microencapsulated feruloyl esterase producing Lactobacillus fermentum ATCC 11976 formulation for use in non-alcoholic fatty liver disease (NAFLD) was investigated. For which Bio F1B Golden Syrian hamsters were fed a methionine deficient/choline devoid diet to induce non-alcoholic fatty liver disease. Results, for the first time, show significant clinical benefits in experimental animals. Examination of lipids show that concentrations of hepatic free cholesterol, esterified cholesterol, triglycerides and phospholipids were significantly lowered in treated animals. In addition, serum total cholesterol, triglycerides, uric acid and insulin resistance were found to decrease in treated animals. Liver histology evaluations showed reduced fat deposits. Western blot analysis shows significant differences in expression levels of key liver enzymes in treated animals. In conclusion, these findings suggest the excellent potential of using an oral probiotic formulation to ameliorate NAFLD.

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease.

BACKGROUND: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology. METHODS: Experiments were planned to develop a diet-induced Bio F(1)B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O. RESULTS: In this study, we established a diet-induced Bio F(1)B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed with a high-fat/high cholesterol diet, as compared to animals fed with the control diet. CONCLUSION: Our study established that hamsters fed with a high-fat/high-cholesterol diet developed fatty liver and mild diabetes. Bio F(1)B hamsters fed with a high-fat/high-cholesterol diet may thus be a good animal model for research on the treatment of diet-induced metabolic syndrome complicated by nonalcoholic fatty liver disease.

Human serum albumin nanoparticles as an efficient noscapine drug delivery system for potential use in breast cancer: preparation and in vitro analysis.

Drug delivery systems such as nanoparticles can provide enhanced efficacy for anticancer agents. Noscapine, a widely used cough suppressant for decades has recently been shown to cause significant inhibition and regression of tumor volumes without any detectable toxicity in cells or tissues. Nanoparticles made of human serum albumin (HSA) represent promising strategy for targeted drug delivery to tumor cells by enhancing the drug's bioavailability and distribution, and reducing the body's response towards drug resistance. In the present study, we report for the first time the incorporation and delivery of noscapine-loaded HSA nanoparticles to tumor cells. The nanoparticles were designed and optimized to achieve a particle size in the range of 150-300 nm with a drug-loading efficiency of 85%-96%. The nanoparticles were evaluated in vitro for their anticancer activity and efficacy on breast cancer cells.

Recombinant baculovirus as a highly potent vector for gene therapy of human colorectal carcinoma: molecular cloning, expression, and in vitro characterization.

Present therapeutic strategies for most cancers are restricted mainly to the primary tumors and are also not very effective in controlling metastatic states. Alternatively, gene therapy can be a potential option for treating such cancers. Currently mammalian viral-based cancer gene therapy is the most popular approach, but the efficacy has been shown to be quite low in clinical trials. In this study, for the first time, the insect cell-specific baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has been evaluated as a vector for gene delivery to colorectal cancer cells. Experiments involving factorial design were employed to study the individual and combined effects of different parameters such as multiplicity of infection (MOI), viral incubation time and epigenetic factors on transduction efficiency. The results demonstrate that baculovirus gene delivery system holds immense potential for development of a new generation of highly effective virotherapy for colorectal, as well as other major carcinomas (breast, pancreas, and brain), and offers significant benefits to traditional animal virus-based vectors with respect to safety concerns.

Ultrafine chitosan nanoparticles as an efficient nucleic acid delivery system targeting neuronal cells.

BACKGROUND: Cell transfection with nanoscaled cationic polymeric particles using Chitosan has been extensively explored. Because of its properties such as cationic charges, biocompatibility, biodegradability, and low toxicity, it has been used as a potential gene, siRNA, protein (including antibodies), and drug carrier system. METHOD: This work describes the development of chitosan nanoparticles of a 20-nm diameter for a potential siRNA delivery application. The particles were prepared using an ionic gelation method, using sodium tripolyphosphate as a cross-linker. The effect of variation in pH was investigated on particle size and surface charge. Gene loading efficiency by chitosan nanoparticles was performed by varying weight ratios of chitosan: siRNA. Transfection efficiency was evaluated on Neuro2a cells. RESULTS: It was observed that 20-nm-sized nanoscale complexes induced significant transfection in neuronal cells. CONCLUSION: These particles have potential in the delivery of siRNA to neural tissues.

Microcapsule carbon nanotube devices for therapeutic applications.

Carbon nanotubes are a new class of nanomaterials that have immense potential in the field of biomedicine. Their ability to carry large quantities of therapeutic molecules makes them prime candidates for providing targeted delivery of therapeutics for use in various diseases. However, their utility is limited due to the problems faced during their delivery to target sites. This article for the first time describes the design of a novel microcapsule carbon nanotube targeted delivery device. This device has potential in the targeted delivery of carbon nanotubes in suitable membranes along with their cargo, safely and effectively to the target loci.

Orally delivered microencapsulated live probiotic formulation lowers serum lipids in hypercholesterolemic hamsters.

Elevated serum cholesterol is a major risk factor for coronary artery disease. Nutritional therapies such as probiotics have been suggested to manage elevated cholesterol. This study investigates the cholesterol and triglyceride lowering potential of a microencapsulated feruloyl esterase-producing Lactobacillus fermentum 11976 (LF11976) probiotic formulation. Male Bio F(1)B hamsters were assigned to two groups to receive either the microcapsule probiotic formulation (containing LF11976 cells at 12.51 log colony-forming units/mL) or placebo formulation (empty) microcapsules, twice daily, by oral gavage for 18 weeks. For the duration of the study, animals were fed a hypercholesterolemic diet. Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and the atherogenic index were 21.36%, 31.43%, and 32.59% lower in the group gavaged with the microencapsulated probiotic formulation than in the placebo control group after 18 weeks (P < .05). Histology studies showed reduced progression of atherosclerotic lesions in animals treated with microencapsulated LF11976 as compared to control animals. Treatment with microencapsulated LF11976 formulation produces significant reductions in serum total cholesterol, LDL cholesterol, and serum triglyceride levels in diet-induced hypercholesterolemic hamsters. Findings suggest the potential of the oral microencapsulated probiotic cell formulation as a functional nutritional alternative for managing excessive serum cholesterol and triglyceride levels.

Preparation and in vitro analysis of microencapsulated live Lactobacillus fermentum 11976 for augmentation of feruloyl esterase in the gastrointestinal tract.

FA (ferulic acid) is a well-known phenolic phytochemical present in plant cell walls. Various studies have indicated that FA has many physiological functions in the prevention of chronic disease. It has been shown to play an important chemoprotective role in degenerative diseases. FA also shows strong antioxidant and nitrite-scavenging potential and anticarcinogenic and antiinflammatory properties. The in vivo physiological importance of FA depends on its availability for absorption. Dietary fibre-bound FA is partially released by gut micro-organisms; however, the concentration of the released FA is too low to act as a chemopreventive agent. Therefore it is important to augment the bioavailability of FA to appreciate more fully its real physiological effect. This paper evaluates the suitability of the alginate-poly(L-lysine)-alginate microcapsules for oral delivery of live feruloyl esterase-producing Lactobacillus fermentum 11976 cells, in vitro, by using a dynamic simulated human GI (gastrointestinal) model. The present study shows that microencapsulated L. fermentum 11976 cells can efficiently break down a FA-containing substrate, and establishes the biotechnological basis for their use in supplementing the bioavailability of dietary FA in the intestine.

Microencapsulated engineered Lactococcus lactis cells for heterologous protein delivery: preparation and in vitro analysis.

This article demonstrates the potential of encapsulated, engineered Lactococcus lactis as a vehicle for the oral delivery of therapeutic proteins. Using alginate-poly-l-lysine-alginate membrane-encapsulated L. lactis engineered to secrete the reporter protein Staphylococcal aureus nuclease, we show comparable viability and protein secretion between free and immobilized cells. After 12 h, microcapsules with a cell density of 4.8 x 10(5) colony forming unit (CFU) ml(-1) grew to 2.2 x 10(8) CFU ml(-1) and released 0.24 arbitrary unit (AU) ml(-1) of nuclease, producing similar results as free cells, which grew from 3.4 x 10(5) to 1.9 x 10(8) CFU ml(-1) and secreted 0.21 AU ml(-1) of nuclease. Moreover, encapsulated cells at a density of 4.4 x 10(7) CFU ml(-1) grew to 2.2 x 10(10) CFU ml(-1) in 12 h and secreted 15.3 AU ml(-1) of nuclease although 3.1 x 10(7) CFU ml(-1)of free cells reached only 2.3 x 10(9) CFU ml(-1) and released 5.6 AU ml(-1) of nuclease. We also show the sustained stability of the microcapsules during storage at 4 degrees C over 8 weeks.

Microencapsulated bacterial cells can be used to produce the enzyme feruloyl esterase: preparation and in-vitro analysis.

Biotechnological production of ferulic acid, a precursor of vanillin, is an attractive alternative for various industries due to the high price and demand for natural ferulic acid. Feruloyl esterase has been identified as a key enzyme involved in microbial transformations of ferulic acid to vanillin. Several fungal feruloyl esterases have been purified and characterized for their use in the production of ferulic acid. This paper, for the first time, discusses the use of lactic acid bacteria for the production of ferulic acid. Specifically, we have used Lactobacillus cells and microencapsulation so that ferulic acid can be produced continuously using various types of fermentation systems. Bacteria were encapsulated in alginate-poly-L-lysine-alginate (APA) microcapsules, and the production of ferulic acid by lactobacilli was detected using a real-time high-performance liquid chromatography (HPLC)-based assay. Results show that ferulic acid can be produced using microencapsulated Lactobacillus fermentum (ATCC 11976) with significant levels of biological feruloyl esterase activity.

Recent advances in drug delivery: potential and limitations of carbon nanotubes.

Outstanding progress has been made in drug delivery approaches. However, challenges still exist in delivering clinically optimal levels of therapeutic molecules. Advances in nanotechnology and nanomedicine have heralded the advent of several innovative nanomaterials which are set to revolutionize the field of drug delivery. Carbon nanotubes are one such novel class of nanomaterials that are gaining increasing attention. They have been modified with several molecules of therapeutic interest. Excellent progress has been made in harnessing the potential of carbon nanotubes for several drug delivery and other applications. Functionalized carbon nanotubes have been demonstrated to deliver proteins, nucleic acids, drugs, antibodies and other therapeutics. Emerging developments in this area are pointing towards the successful utilization of carbon nanotubes for drug delivery. This review presents a comprehensive summary of the recent patents in carbon nanotube mediated drug delivery systems, their clinical significance, limitations and future prospects.