No abstract

No abstract

No abstract

This review covers the current aspects of leishmaniasis including marketed drugs, new antileishmanial agents, and possible drug targets of antileishmanial agents.

Gene therapy is a powerful approach in the treatment of a wide range of both inherited and acquired diseases. Nonviral delivery systems have been proposed as safer alternatives to viral vectors because they avoid the inherent immunogenicity and production problems that are seen when viral systems are used. Many cationic polymers, including high-molecular-weight polyethylenimine (PEI) have been widely studied as gene-delivery carriers, both, in vitro and in vivo. However, interest has recently developed in degradable polymeric systems. The advantage of degradable polymer is its low in-vivo cytotoxicity, which is a result of its easy elimination from the cells and body. Degradable polymer also enhances transfection of DNA or small interfering RNA (siRNA) for efficient gene expression or silencing, respectively. This review paper summarizes and discusses the recent advances with degradable PEIs, such as cross-linked and grafted PEIs for DNA and siRNA delivery.

No abstract

Chitosans have been proposed as alternative, biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan need to be addressed before clinical application. We prepared galactosylated chitosan-graft-polyethylenimine (GC-g-PEI) copolymer by an imine reaction between periodate-oxidized GC and low-molecular-weight PEI. The molecular weight and composition were characterized using gel permeation chromatography column with multi-angle laser scattering and (1)H nuclear magnetic resonance, respectively. The copolymer was complexed with plasmid DNA in various copolymer/DNA (N/P) charge ratios, and the complexes were characterized. GC-g-PEI showed good DNA-binding ability and superior protection of DNA from nuclease attack and had low cytotoxicity compared to PEI 25K. GC-g-PEI/DNA complexes showed higher transfection efficiency than PEI 25K in both HepG2 and HeLa cell lines. Transfection efficiency into HepG2, which has asialoglycoprotein receptors, was higher than that into HeLa, which does not. GC-g-PEI/DNA complexes also transfected liver cells in vivo after intraperitoneal (i.p.) administration more effectively than PEI 25K. These results suggest that GC-g-PEI can be used in gene therapy to improve transfection efficiency and hepatocyte specificity in vitro and in vivo.

Despite the immense potential of non-viral delivery system in gene therapy its application has been impaired greatly by various impediments having contrasting traits. Therefore it is an absolute necessity to develop some non-viral vectors which are endowed with special characteristics to act differently in intracellular as well as extracellular compartments to surmount these inter-conflicting hurdles. Such smart polymers should serve some specific purposes by adjusting their structural or functional traits under the influence of stimuli such as temperature, light, salt concentration or pH. Among all these stimuli-responsive polymers pH-responsive polymers have attracted major attention and great impetus has been directed towards utilizing the subtle yet significant change in pH value within the cellular compartments. This review is intended to provide a comprehensive account of the development of pH-responsive polymeric vectors based on their structural features and consequent functional attributes to achieve efficient transfection. The underlying modes of actions relating to structure and differential pH environment have also been discussed in this review.