Maroof Alam

Development, characterization and efficacy of niosomal diallyl disulfide in treatment of disseminated murine candidiasis

UNLABELLED In the current study, a novel niosome based formulation of diallyl disulfide (DADS) was evaluated for its potential to treat disseminated candidiasis in mouse model. Among various non-ionic surfactants tested, niosome formulation prepared using Span 80 was found to be most efficient in the entrapment of DADS. The DADS loaded niosomes had size dimensions in the range of 140 ± 30 nm with zeta potential of -30.67 ± 4.5. Liver/kidney function tests as well as histopathologic studies suggested that noisome-based DADS formulations are safe at the dose investigated. When administered to Candida albicans infected animals, the DADS bearing niosomal formulation cleared the fungal burden and increased their survival much efficiently than its free form. FROM THE CLINICAL EDITOR In this study, a novel niosomal formulation of the antifungal DADS was utilized in a murine candidiasis model, resulting in more efficient fungal clearance compared to the free formulation.

Efficacy of niosomal formulation of diallyl sulfide against experimental candidiasis in Swiss albino mice

AIM We developed a niosomal formulation of diallyl sulfide (DAS), a garlic oil component, and evaluated its efficacy against experimental candidiasis in mice. METHODS DAS-bearing niosomes prepared from sorbitan monoester surfactants were evaluated for drug entrapment efficiency, release kinetics, toxicity, size, zeta-potential and others. Mice challenged with Candida albicans were treated with various DAS formulations. The efficacy of the formulations was assessed on the basis of reduction in mortality and decrease in residual fungal load in vital organs, such as liver and spleen, of treated mice. RESULTS Niosomal DAS (12 mg/kg body weight) significantly reduced fungal load and mortality in treated animals compared with the free form of DAS. Niosomal DAS was also found to be free of toxic manifestations, as revealed by histopathological studies, as well as liver/kidney function tests. CONCLUSION Incorporation of DAS in niosomes enhances its antifungal efficacy. Further studies are needed to optimize the current findings to develop an efficient nature-derived alternative antifungal therapeutic strategy.

Efficacy of amoxicillin bearing microsphere formulation in treatment of Listeria monocytogenes infection in Swiss albino mice.

The present study deals with the evaluation of the efficacy of amoxicillin bearing poly-lactic-glycolic acid (PLGA) microsphere formulation in treatment of experimental listeriosis in Swiss albino mice. Amoxicillin bearing PLGA microspheres were prepared by water-in-oil-in-water emulsion technique. PLGA microwspheres significantly regulated sustained release of encapsulated drug over extended time period. The rate of release increased in temperature dependent manner. Amoxicillin bearing PLGA microsphere successfully cleared bacterial burdens in vital organs (kidney, spleen, and brain) and also increased survival rate of treated animals in comparison to free form of the drug. The higher efficacy of microsphere based novel formulation of amoxicillin could be attributed to its targeted delivery to infected macrophages as well as sustained release over extended period of time.

A rabbit eye model for in vivo transformation of progenetic metacercariae of Clinostomum complanatum into ovigerous adult worms

Clinostomum complanatum is a digenetic trematode that causes yellow grub disease in some fish species and also shows zoonotic potential by sporadically infecting humans. In this study, progenetic metacercariae of C. complanatum were obtained from the fish Trichogaster fasciatus, and were aseptically placed in conjunctival incisions made in the superior and inferior fornices of the eye of rabbits, which served as the experimental hosts. Worms were harvested without necropsy of the host on days 4 and 8 post infection, to observe in vivo transformation of the progenetic metacercariae into ovigerous adult worms. The worms appeared to cause minimal damage to the host although they were tenaciously attached. In vivo maturation was evident by the development of the vitellaria, enlargement of gonads, the presence of a large number of shelled eggs in a distended uterus and ramifications of the intestinal caeca. Obtaining mature ovigerous worms without sacrificing the host clearly gives the rabbit eye model an advantage over those described previously. Due to the relative advantage of the short time required for maturation and the prolific egg production by C. complanatum, it is suggested that this host-parasite system could be used as an excellent model for classroom teaching of trematode biology and to investigate the cues involved in in vivo transformation and host-parasite interactions.

Levels of some antioxidant molecules and lipid peroxidation during in vivo transformation of the progenetic metacercaria of Clinostomum complanatum to ovigerous adult worms.

The levels of oxidative stress markers are an important indicator of the physiological state of the parasite and its host. In the present study levels of lipid peroxidation, glutathione S transferase, glutathione, superoxide dismutase and catalase were determined in the Clinostomum complanatum progenetic metacercaria, obtained from the fish peritoneum (a hypoxic habitat). The in vivo transformed ovigerous adult worms were obtained from the aerobic environment of the buccopharyngeal region of experimentally infected chickens. Levels of antioxidant molecules were also determined in the blood of experimentally infected chickens. An increase in the levels of lipid peroxidation, and a significant decrease in the levels of glutathione S transferase, glutathione, superoxide dismutase and catalase was observed in the infected host as compared to the controls. In the ovigerous worms, the levels of lipid peroxidation, glutathione S transferase, glutathione, superoxide dismutase were found to be significantly less than the levels observed in the progenetic metacercaria. Since the establishment of worm in the buccal cavity of the avian host would lead to its exposure to oxygen and the haematophagous nature of the parasite also exposes it to the free radicals in the host blood, the progenetic metacercaria has evolved to produce excess free radical scavenging molecules reserved to combat the oxidative stress encountered within the microhabitat of the definitive host.

Novel Drug Delivery Systems for Antifungal Compounds

Development of new approaches for treatment of invasive fungal infections encompasses new delivery systems for approved and investigational compounds. Novel delivery systems consisting of cyclodextrins (CDs), cochleates, nanoparticles, and long-circulating (“stealth”) liposomes modulate the pharmacokinetics of existing drugs, and may also be useful to enhance the delivery of antifungal agents to sites of infection. Among several promising new drug-delivery systems, liposomes represent an advanced technology for site-directed delivery of active molecules. Research on liposome technology has progressed from conventional vesicles (“first-generation liposomes”) to “second-generation liposomes,” in which long-circulating liposomes are obtained by modifying the surface of liposomes using several molecules, such as glycolipids, sialic acid, or synthetic polymer poly-(ethylene glycol) (PEG), resulting in prolonged reticulo-endothelial system uptake and serum half-life, thus increasing the therapeutic efficacy of drugs. At present, several formulations for amphotericin B are in clinical use for fungal infections in Europe and the United States. Nanoformulations have also been applied as drug delivery systems (DDSs), with great success. Finally, progress in the design of DDSs has led to the development of carriers targeted to specific tissues and cells. Efforts are now going on to improve their stability in the biological environment, to mediate the biodistribution of active compounds, and to improve drug loading, targeting, transport, release, and interaction with biological barriers. This chapter discusses the state of the art in the field of DDSs, used for control of systemic fungal infections.

Immunomodulators: Potential in Treatment of Systemic Fungal Infections

Innate immunity mediates strong resistance to fungal pathogens and contributes to host defense against opportunistic fungal infections such as candidiasis, aspergillosis, and other rare infections. Immune factors such as cytokines and effector immune cells work synergistically with antifungal agents to restrict fungal growth. However, in immunocompromised hosts, the defectiveness of immune functions that should cooperate with antifungal drugs to clear the pathogens seems to be a critical factor that impedes the effectiveness of these drugs. The renovation or augmentation of immune responses is now considered as one of the foundations of effective antifungal therapy. Immunomodulation represents a novel approach to antimicrobial therapy that depends on boosting host immunity, rather than direct antimicrobial activity. Immunopotential therapy therefore offers a rational approach to the treatment of fungal infections, because it is intended to enhance immune functions in general. Major advances in the field of experimental immunology have provided insight into the important regulatory role of cytokines in both innate and adaptive immunity to fungal pathogens. Exploration has also begun with immunotherapy, with use of cytokines and immunomodulators alone or in combination with antifungal therapy. The administration of cytokines to patients, together with antifungal agents, offers promising immuno-therapeutic modalities for further research. The diverse array of natural, synthetic, and recombinant immunomodulators discussed in this chapter succinctly demonstrates the potential of these agents to stimulate host defense mechanisms for prophylaxis and treatment of various fungal infections.

Therapeutic effect of vitamin B 3 on hyperglycemia, oxidative stress and DNA damage in alloxan induced diabetic rat model

Evidences in the form of experimental analysis and scientific investigations suggest that oxidative stress embody an imperative role in the onset and progression of type-2 diabetes mellitus (T2DM). Aberrant elevation in levels of free radicals, as observed upon disease onset, and the subsequent reduction in anti-oxidant defenses is pernicious to metabolic enzymes and cellular organelles. Niacin (Vitamin B3) is an essential nutrient for humans and is considered to be an important food additive for animals too. This research was conducted to examine the effect of nutraceutical antioxidant on diabetic environment. This important member of Vitamin B complex is a forerunner of nicotinamide adenine dinucleotide (NAD) and also nicotinamide adenine dinucleotide phosphate (NADP), both of them serving as coenzymes for several metabolic enzymes. This study reports the effects of niacin supplementation in alloxan induced diabetic rats divided into five groups. Diabetes induced rats were further treated with niacin at two doses (10 and 15 mg /kg body weight) and compared with a control set of diabetes without treatment. Niacin treatment showed recovery in almost all parameters in a dose reliant pattern. A notable decline in oxidative stress parameters with reductions in fasting blood glucose levels was observed. Histological studies reveal damage recovery in the liver as well as kidney tissues. A notable amount of recovery was observed in cellular DNA damage. As a deduction, it is advocated that dietary niacin supplementation might help in reducing problems associated with diabetes. A probable mechanism pertaining to the action of niacin is proposed as well.