Sudesh Kumar Yadav

Biodegradable polymeric nanoparticles based drug delivery systems

Biodegradable nanoparticles have been used frequently as drug delivery vehicles due to its grand bioavailability, better encapsulation, control release and less toxic properties. Various nanoparticulate systems, general synthesis and encapsulation process, control release and improvement of therapeutic value of nanoencapsulated drugs are covered in this review. We have highlighted the impact of nanoencapsulation of various disease related drugs on biodegradable nanoparticles such as PLGA, PLA, chitosan, gelatin, polycaprolactone and poly-alkyl-cyanoacrylates.

Development of biodegradable nanoparticles for delivery of quercetin.

The antioxidant molecule quercetin has been encapsulated on poly-D,L-lactide (PLA) nanoparticles by solvent evaporation method for the improvement of its poor aqueous solubility and stability. The surface morphology and average size of PLA and quercetin loaded PLA nanoparticles are 170+/-25 and 130+/-30 nm respectively. The antioxidant activities of the PLA encapsulated quercetin nanomedicine are identical to free quercetin. The nanoencapsulation efficiency of quercetin evaluated by HPLC and antioxidant assay is 96.7%. The in vitro release kinetics under physiological condition show initial burst release followed by slow and sustained release. The complete release and maximum retention of quercetin is 72 and 96h respectively. The less fluorescence quenching efficiency of quercetin-PLA nanoparticles than free quercetin on BSA confirms the controlled release of quercetin from PLA nanoparticles. These properties of PLA encapsulated quercetin molecule pave way for encapsulating various therapeutically less useful highly active antioxidant molecules towards the development of better therapeutic compounds.

Cold stress tolerance mechanisms in plants. A review

The human population is increasing at an alarming rate, whereas at the same time agricultural productivity is decreasing due to the effect of various environmental problems. In particular, cold stress is a serious threat to the sustainability of crop yields. Indeed, cold stress can lead to major crop losses. Various phenotypic symptoms in response to cold stress include poor germination, stunted seedlings, yellowing of leaves (chlorosis), reduced leaf expansion and wilting, and may lead to death of tissue (necrosis). Cold stress also severely hampers the reproductive development of plants. The major negative effect of cold stress is that it induces severe membrane damage. This damage is largely due to the acute dehydration associated with freezing during cold stress. Cold stress is perceived by the receptor at the cell membrane. Then a signal is transduced to switch on the cold-responsive genes and transcription factors for mediating stress tolerance. Understanding the mechanism of cold stress tolerance and genes involved in the cold stress signaling network is important for crop improvement. Here, I review cold stress tolerance mechanisms in plants. The major points discussed are the following: (1) physiological effects of cold stress, (2) sensing of cold temperatures and signal transduction, and (3) the role of various cold-responsive genes and transcription factors in the mechanism of cold stress tolerance.

Nanoencapsulation and characterization of Albizia chinensis isolated antioxidant quercitrin on PLA nanoparticles

The plant isolated antioxidant quercitrin has been encapsulated on poly-d,l-lactide (PLA) nanoparticles by solvent evaporation method to improve the solubility, permeability and stability of this molecule. The size of quercitrin-PLA nanoparticles is 250±68nm whereas that PLA nanoparticles is 195 ± 55nm. The encapsulation efficiency of nanoencapsulated quercitrin evaluated by HPLC and antioxidant assay is 40%. The in vitro release kinetics of quercitrin under physiological condition reveals initial burst release followed by sustained release. Less fluorescence quenching is observed with equimolar concentration of PLA encapsulated quercitrin than free quercitrin. The presence of quercitrin specific peaks on FTIR of five times washed quercitrin loaded PLA nanoparticles provides an extra evidence for the encapsulation of quercitrin into PLA nanoparticles. These properties of quercitrin nanomedicine provide a new potential for the use of such less useful highly active antioxidant molecule towards the development of better therapeutic for intestinal anti-inflammatory effect and nutraceutical compounds.

Cellular interactions of therapeutically delivered nanoparticles

Introduction: Nanoparticles (NPs) are used extensively in drug delivery. They are administered through various routes in the host, and their uptake by the cellular environment has been observed in several pathways. After uptake, NPs interact with cells to different extents, depending on their size, shape, surface properties, ligands tagged to the surface and tumor architecture. Complete understanding of such cellular uptake mechanisms and interactions of NPs is important for their effective use in drug delivery. Areas covered: This article describes the various cellular pathways for NP uptake, and the factors affecting NP uptake and interactions with cells. Understanding these two important aspects will help in the future design of NPs for effective and targeted drug delivery. Expert opinion: Surface charge and ligands tagged on the surface of NPs play a critical role in their uptake and interaction with cells; so surface modifications of NPs can offer increased drug delivery effectiveness, for example, the coupling of ligands on the surface of NPs can increase cellular binding, and NPs in biological fluids can be coated with proteins and as such can exert biological effects. All of the factors affecting NP uptake need to be investigated thoroughly before interpreting any NP–cellular interactions.

Evaluating the Toxicity of Selected Types of Nanochemicals

Nanotechnology is a fast growing field that provides for the development of materials that have new dimensions, novel properties, and a broader array of applications. Various scientific groups are keen about this technology and are devoting themselves to the development of more, new, and better nanomaterials. In the near future, expectations are that no field will be left untouched by the magical benefits available through application of nanotechnology. Presently, there is only limited knowledge concerning the toxicological effects of NPs. However, it is now known that the toxic behavior of NPs differ from their bulk counterparts. Even NPs that have the same chemical composition differ in their toxicological properties; the differences in toxicity depend upon size, shape, and surface covering. Hence, before NPs are commercially used it is most important that they be subjected to appropriate toxicity evaluation. Among the parameters of NPs that must be evaluated for their effect on toxicity are surface charges, types of coating material, and reactivity of NPs. In this article, we have reviewed the literature pertinent to the toxicity of metal oxide NPs, metallic NPs, quantum dots (QDs), silica (SiO2) NPs, carbon nanotubes (CNTs), and certain other carbon nanomaterials (NMs). These NPs have already found a wide range of applications around the world. In vitro and in vivo studies on NPs have revealed that most are toxic to animals. However, their toxic behavior varies with their size, shape, surface charge, type of coating material and reactivity. Dose, route of administration, and exposure are critical factors that affect the degree of toxicity produced by any particular type of NP. It is for this reason that we believe a careful and rigorous toxicity testing is necessary before any NP is declared to be safe for broad use. We also believe that an agreed upon testing system is needed that can be used to suitably, accurately, and economically assess the toxicity of NPs. NPs have produced an array of different toxic effects in many different types of in vivo and in vitro studies. The types of effects that NPs have produced are those on the pulmonary, cardiac, reproductive, renal and cutaneous systems, as well as on various cell lines. After exposures, significant accumulations of NPs have been found in the lungs, brain, liver, spleen, and bones of test species. It has been well established that the degree of toxicity produced by NPs is linked to their surface properties. Soluble NPs are rendered toxic because of their constituents; however, the situation is entirely different for insoluble NPs. Stable metal oxides do not show any toxicity, whereas metallic NPs that have redox potential may be cytotoxic and genotoxic. The available data on NP toxicity is unfortunately limited, and hence, does not allow scientists to yet make a significant quantitative risk assessment of the safety of synthesized NPs. In this review, we have endeavored to illustrate the importance of having and using results from existing nanotoxicological studies and for developing new and more useful future risk assessment systems. Increased efforts of both an individual and collective nature are required to explore the future pros and cons of nanotechnology.

Steviol Glycosides from Stevia: Biosynthesis Pathway Review and their Application in Foods and Medicine

Stevia rebaudiana, a perennial herb from the Asteraceae family, is known to the scientific world for its sweetness and steviol glycosides (SGs). SGs are the secondary metabolites responsible for the sweetness of Stevia. They are synthesized by SG biosynthesis pathway operating in the leaves. Most of the genes encoding the enzymes of this pathway have been cloned and characterized from Stevia. Out of various SGs, stevioside and rebaudioside A are the major metabolites. SGs including stevioside have also been synthesized by enzymes and microbial agents. These are non-mutagenic, non-toxic, antimicrobial, and do not show any remarkable side-effects upon consumption. Stevioside has many medical applications and its role against diabetes is most important. SGs have made Stevia an important part of the medicinal world as well as the food and beverage industry. This article presents an overview on Stevia and the importance of SGs.

Plant Small RNAs:Biogenesis, Mode of Action and Their Roles in Abiotic Stresses

Small RNAs (sRNAs) are 18-30 nt non-coding regulatory elements found in diverse organisms, which were initially identified as small double-stranded RNAs in Caenorhabditis elegans. With the development of new and improved technologies, sRNAs have also been identified and characterized in plant systems. Among them, micro RNAs (miRNAs) and small interfering RNAs (siRNAs) are found to be very important riboregulators in plants. Various types of sRNAs differ in their mode of biogenesis and in their function of gene regulation. sRNAs are involved in gene regulation at both transcriptional and post-transcriptional levels. They are known to regulate growth and development of plants. Furthermore, sRNAs especially plant miRNAs have been found to be involved in various stress responses, such as oxidative, mineral nutrient deficiency, dehydration, and even mechanical stimulus. Therefore, in the present review, we focus on the current understanding of biogenesis and regulatory mechanisms of plant sRNAs and their responses to various abiotic stresses.

Isolation of a Psychrotrophic Exiguobacterium sp. SKPB5 (MTCC 7803) and Characterization of Its Alkaline Protease

Out of nine psychrotrophic bacterial strains isolated from cold environments of the Western Himalayas, SKPB5 was selected for protease purification and characterization because it had the largest zone of clearance on plate assay. On the basis of the phenotypic and biochemical characterization and 16S rRNA gene-sequencing studies, isolate was identified as Exiguobacterium sp. SKPB5. The protease was purified near to homogeneity with a purification fold of 7.1, and its molecular weight was determined to be 36 kDa. The enzyme exhibited maximum stability at 50°C and an optimal pH of 8.0. Metal ions Mg2+, Ca2+, Zn2+, and Mn2+ enhanced the enzyme activity, whereas Cu2+ had no effect. Phenylmethanesulfonyl fluoride and ethylenediaminetetraacetic acid did not show any effect on the activity of the enzyme, whereas a 20% increase in activity was observed when it was incubated in presence of reducing agents such as β-mercaptoethanol and dithiothreitol. This suggests that the protease isolated from psychrotrophic Exiguobacterium sp. SKPB5 belongs to the cysteine family. The results highlight the relevance of unexplored microbes from cold environments of Western Himalayas for the isolation of protease enzymes active at wide range of temperature and pH.

Gold nanoparticle exposure induces growth and yield enhancement in Arabidopsis thaliana.

Nanotechnology has the potential to revolutionize agriculture field. Towards this effort, carbon nanotubes have recently been reported to induce growth enhancement of tobacco cells. In this study, exposure to 24 nm size gold nanoparticles (GNPs) at 10 μg/ml concentration was found to enhance the total seed yield of Arabidopsis thaliana by 3 times over the control. In addition, 24 nm size GNP exposure at both 10 and 80 μg/ml concentrations has significantly improved seed germination rate, vegetative growth and free radical scavenging activity. A considerable correlation was found between expression of key plant regulatory molecules, microRNAs (miRs) and seed germination, growth and antioxidant potential of A. thaliana on GNP exposure. This is the first report showing GNPs as a promising tool to enhance seed yield of plants.