Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic analogues, belong to the flavonoid family, which possess a number of interesting biological properties such as antioxidant, cytotoxic, anticancer, antimicrobial, antiprotozoal, antiulcer, antihistaminic and anti-inflammatory activities. Several pure chalcones have been approved for clinical use or tested in humans. Clinical trials have shown that these compounds reached reasonable plasma concentration and are well-tolerated. For this reason they are an object of continuously growing interest amongst the scientists. However, much of the pharmacological potential of chalcones is still not utilized. The purpose of this review is to provide an overview of the pharmacological activity of naturally occurring and synthetic chalcones. This review highlights more recent pharmacological screening of these compounds, their mechanisms of action and relevant structure-activity relationships.

The uptake of vitamin B12 (cyanocobalamin, Cbl/VB12) in mammalian cells is mediated by specific, high-affinity receptors for the vitamin B12-binding protein, transcobalamin II, which is expressed on the plasma membrane. The receptor for vitamin B12 is overexpressed on a number of human tumors, including cancers of the ovary, kidney, uterus, testis, brain, colon, lung, and myelocytic blood cells. Furthermore, the affinity of cyanocobalamin conjugates for cell surface transcobalamin II receptors seems to be high enough so that vitamin B12 derivatization with the cytotoxic agent or carriers bearing cytotoxic drugs allows the selective delivery of diagnostic and therapeutic agents to cancer cells. Thus, conjugates of vitamin B12 enter receptor-expressing cancer cells via receptor-mediated endocytosis, and targeting may be accomplished by multiple mechanisms, depending on the drug-delivery strategy. This review summarizes the applications of vitamin B12 as a targeting ligand and highlights the various methods being developed for delivery of therapeutic and imaging agents to cancer cells in vitro and in vivo. This review reflects the potentiality of vitamin B12 for tumor targeting of chemotherapeutic and diagnostic agents.

Diseases and disorders of the brain are extremely difficult to treat pharmacologically because most drugs are unable to pass across the blood--brain barriers. Complex multi-strand tight junctions between adjacent cerebral endothelial cells and between choroid plexus epithelial cells form a physical barrier and prevent the passage of water soluble drugs from the blood into the brain, whereas the inward passage of lipid soluble drugs is restricted by drug efflux pumps which act as a functional barrier. In the present work, a transferrin-coupled liposomal system for brain delivery of 5-florouracil has been investigated.5-florouracil and (99m)Tc-DTPA bearing non-coupled liposomes were prepared by cast film method, which were coupled with the transferrin by incubating these liposomes with transferrin in the presence of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in saline phosphate buffer (pH 7.4). These liposomal systems were characterized for vesicle size, percent drug entrapment, and in vitro drug release. The size of the liposomes was increased on coupling with transferrin while percent drug entrapment reduced. The results of the in vitro release profile demonstrated that non-coupled liposomal formulation releases a comparatively higher percent (i.e. 74.8+/-3.21%) of drug than coupled liposomes. Results of in vivo study suggested a selective uptake of the transferrin-coupled liposomes from the brain capillary endothelial cells. In case of coupled liposomes, the level of radioactivity was 17-fold more as compared to the free radioactive agent and 13 times more with the non-coupled liposomes. Therefore, it could be concluded that using transferrin coupled liposomes the brain uptake of the drug could be enhanced.

This review deals with the antisense technology that, together, forms a very powerful tool to inhibit gene expression and may be used for studying gene function (functional genomics) and for therapeutic purpose (antisense gene therapy). Antisense oligonucleotides block translation of target mRNAs in a sequence specific manner, either by steric blocking of translation or by destruction of the bound mRNA via RNase-H enzyme. For proper designing, accessible sites of the target RNA for binding antisense oligonucleotides have to be identified. Whether being used as an experimental reagent or pharmaceuticals, several problems or drawbacks have to be overcome for successful applications. Toward this direction, various modifications of sugar, bases and phosphate backbone of antisense oligonucleotides have been attempted. In recent years valuable progress has been achieved through the development of advanced cellular delivery systems and novel chemically modified nucleotides with improved properties such as enhanced serum stability, higher target affinity and low toxicity. These qualities and the specificity of binding make this technique a potentially powerful therapeutic tool for gene targeting and/ or expression regulation. This review discusses the basis of structural design, mode of action, chemical modification, enhanced cellular uptake, therapeutic application and future possibilities in the field of advanced antisense technology.

The therapeutic potential of antisense oligonucleotides (ASODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study focuses on designing mannosylated low molecular weight (LMW) chitosan nanoconstructs for safe ODNs delivery by macrophage targeting. Mannose groups were coupled with LMW chitosan and characterized spectroscopically. Mannosylated chitosan ODN nanoparticles (MCHODN NPs) were formulated by self-assembled method using various N/P ratio (moles of amine groups of MCH to phosphate moieties of ODNs) and characterized for gel retardation assay, physicochemical characteristics, cytotoxicity and transfection efficiency, and antisense assay. Complete complexation of MCH/ODN was achieved at charge ratio of 1:1 and above. On increasing the N/P ratio of MCH/ODN, particle size of the NPs decreased whereas zeta potential (ZV) increased. MCHODN NPs displayed much higher transfection efficiency into Raw 264.7 cells (bears mannose receptors) than Hela cells and no significant toxicity was observed at all MCH concentrations. Antisense assay revealed that reduction in lipopolysaccharide (LPS) induced serum TNF-α is due to antisense activity of TJU-2755 ODN (sequence complementary to 3′-UTR of TNF-α). These results suggest that MCHODN NPs are acceptable choice to improve transfection efficiency in vitro and in vivo.