Poly propyl ether imine (PETIM) dendrimer: A novel non-toxic dendrimer for sustained drug delivery

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
European Journal of Medicinal Chemistry (Impact Factor: 3.45). 11/2010; 45(11):4997-5005. DOI: 10.1016/j.ejmech.2010.08.006
Source: PubMed


In the present study, an attempt was made to study the acute and sub-acute toxicity profile of G3-COOH Poly (propyl ether imine) [PETIM] dendrimer and its use as a carrier for sustained delivery of model drug ketoprofen. Drug-dendrimer complex was prepared and characterized by FTIR, solubility and in vitro drug release study. PETIM dendrimer was found to have significantly less toxicity in A541 cells compared to Poly amido amine (PAMAM) dendrimer. Further, acute and 28 days sub-acute toxicity measurement in mice showed no mortality, hematological, biochemical or histopathological changes up to 80 mg/kg dose of PETIM dendrimer. The results of study demonstrated that G3-COOH PETIM dendrimer can be used as a safe and efficient vehicle for sustained drug delivery.

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    • "Purity by HPLC-CAD was 97% (Fig 3C). PETIM(COOH ) 16 dendrimer has been shown previously not to be toxic in vivo (Jain et al, 2010). "
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    ABSTRACT: Intestinal pathogens use the host's excessive inflammatory cytokine response, designed to eliminate dangerous bacteria, to disrupt epithelial gut wall integrity and promote their tissue invasion. We sought to develop a non-antibiotic-based approach to prevent this injury. Molecular docking studies suggested that glycosylated dendrimers block the TLR4-MD-2-LPS complex, and a 13.6 kDa polyamidoamine (PAMAM) dendrimer glucosamine (DG) reduced the induction of human monocyte interleukin (IL)-6 by Gram-negative bacteria. In a rabbit model of shigellosis, PAMAM-DG prevented epithelial gut wall damage and intestinal villous destruction, reduced local IL-6 and IL-8 expression, and minimized bacterial invasion. Computational modelling studies identified a 3.3 kDa polypropyletherimine (PETIM)-DG as the smallest likely bioactive molecule. In human monocytes, high purity PETIM-DG potently inhibited Shigella Lipid A-induced IL-6 expression. In rabbits, PETIM-DG prevented Shigella-induced epithelial gut wall damage, reduced local IL-6 and IL-8 expression, and minimized bacterial invasion. There was no change in β-defensin, IL-10, interferon-β, transforming growth factor-β, CD3 or FoxP3 expression. Small and orally delivered DG could be useful for preventing gut wall tissue damage in a wide spectrum of infectious diarrhoeal diseases. –>See accompanying article
    Full-text · Article · Sep 2012 · EMBO Molecular Medicine
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    • "For example, a polymeric micelle formulation containing paclitaxel was tested for pancreatic, colonic, and gastric tumor treatments [19]. Lastly, dendrimers , with branched monomer units, possess great potential in conjugating drugs and ligands to lead to possible improvement in controlled and targeted DDSs [20].These important particulate DDSs are briefly reviewed to illustrate conventional ap- proaches. "
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    ABSTRACT: Micro- and nanoparticulate drug-delivery systems (DDSs) play a significant role in formulation sciences. Most particulate DDSs are scaffold-free, although some particles are encapsulated inside other biomaterials for controlled release. Despite rapid progress in recent years, challenges still remain in controlling the homogenicity of micro-/nanoparticles, especially for two crucial factors in particulate DDSs: the size and shape of the particles. Recent approaches make use of microfabrication techniques to generate micro-/nanoparticles with highly controllable architectures free of scaffolds. This review presents an overview of a burgeoning field of DDSs, which can potentially overcome some drawbacks of conventional techniques for particle fabrication and offer better control of particulate DDSs.
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    ABSTRACT: This concise review focuses on dendrimers functionalized by different linkers required for covalent and ionic attachments of drugs to the dendrimer's surface and highlights the importance of the chemical nature of linkers for controlled release of free drugs. The stability of linkers under physiological conditions and their lability under acidic conditions such as those of endosomes and lysosomes or under enzymatic conditions will be discussed. Especially, we review functionality of the most recently reported drug–dendrimer conjugates. Then, we give a short comparison of dendrimer conjugates versus either dendrimer complexes or polymer therapeutics and finally we briefly summarize the importance of both targeted and nontargeted covalently conjugated drugs.
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