The development of dendritic architecture with well-defined size, shape and controlled exterior functionality holds promise in pharmaceutical applications such as drug delivery, solubilization, DNA transfection and diagnosis. Highly branched, monodisperse, stable molecular level and low polydispersity with micelle-like behavior possessing nano-scale container property distinguish these structures as inimitable and optimum carrier for those applications. However reticuloendothelial system (RES) uptake, drug leakage, immunogenicity, hemolytic toxicity, cytotoxicity, hydrophobicity restrict the use of these nanostructures. PEGylation of dendrimers can generally overcome these shortcomings. Hemolytic and different cell line studies have shown reduced toxicity of PEGylated dendrimers than cationic dendrimers. PEGylation causes increased solubilization of hydrophobic drugs in dendritic framework as well as in PEG layers. PEGylated dendrimers have proved capable of forming stable complex with plasmid DNA and achieved improved gene transfection as compared to non-PEGylated dendrimers. Attachments of targeting moiety on the surface of partially PEGylated dendrimer created much interest as a delivery system for crossing of biological barriers and deliver the bioactive agent near the vicinity of target site. Recent successes also demonstrate potential of PEGylated dendrimers as magnetic resonance imaging contrast agent and in carbonyl metallo immunoassay. This review focuses on the current state of the art in the field and focuses on the potential of PEGylated dendrimers in pharmaceutical and biomedical area.
Despite the fact that we live in an era of advanced technology and innovation, infectious diseases, like Tuberculosis (TB), continue to be one of the greatest health challenges worldwide. The main drawbacks of conventional TB treatment are the development of multiple drug resistance, resulting in high dose requirements and subsequent intolerable toxicity. Therefore there is a need of a new system have been receiving special attention with the aim of minimizing the side effects of drug therapy, such as poor bioavailability and the selectivity of drugs. Nanoparticle-based drug delivery systems have considerable potential for treatment of TB. The important technological advantages of nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation. Nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix. These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency, and may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for TB.
Cancer treatment using siRNA based therapies pose various limitations such as off-target effects and degradation due to lack of specific delivery in desired cells. The aim of the present study was to develop multifunctional targeted nanoconstructs, which can efficiently and precisely deliver siRNA and silence the desired gene of interest in various LHRH overexpressing cancer cells. Herein, we report the development of triblock, PAMAM-histidine-PEG dendritic nanoconstructs functionalized with triptorelin (an LHRH analog) for targeted siRNA delivery to LHRH overexpressing breast (MCF-7) and prostate (LNCaP) cancer cells. The nanoconstructs were characterized using H NMR and DLS and displayed a very low cationic charge to avoid off-target interactions. The developed nanoconstructs showed negligible cytotoxicity and hemolytic activity with efficient siRNA loading, excellent serum stability, and strongly protected siRNA from degradation. Further, confocal microscopy results confirmed extremely significant (p< 0.001) higher cellular uptake of cy5.5 conjugated targeted nanoparticles (NPs) in both cancer cell lines than nontargeted NPs. Also, targeted NPs specifically delivered cy3-tagged siRNA to MCF-7 cells. Co-localization studies in MCF-7 and LNCaP cells further established that targeted NPs traveled through the endolysosomal pathway and escaped endosomes within 6 h of incubation. Gene silencing studies in luciferase expressing MCF-7 and LNCaP cell lines demonstrated that the targeted NPs exhibited extremely significant (p < 0.001) silencing of luciferase gene. Additionally, receptor blockade studies further confirmed the specificity of targeted NPs and suggested that targeted NPs entered cancer cells via LHRH receptor mediated endocytosis, which was evident through insignificant gene silencing in receptor blocked cells. Thus, the results indicated that PAMAM-histidine-PEG-triptorelin could be a promising approach for siRNA delivery, gene silencing, and tumor therapy in all LHRH overexpressing cancer cells.
The modulatory potential of Spirulina fusiformis was observed on the hepatic and extrahepatic carcinogen metabolizing enzymes in Swiss albino mice at a dose of 800 mg/kg b.w. given orally. A significant reduction in the hepatic cytochrome P-450 content was observed in the group treated with Spirulina in comparison with the control group. The hepatic glutathione S-transferase activity was induced significantly by Spirulina treatment. There was no change in the extrahepatic glutathione S-transferase activity after the animals were fed with Spirulina.
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