Cyclodextrins cell targeting

Fig. 23 In vivo performance of targeted cyclodextrin polycations, (a) Growth curves for engrafted tumors. The median integrated tumor bioluminescent signal (photons/s) for each treatment group (n = 8-10) is plotted vs time after cell injection (days), (b) MRI confirmation of tumor engraft-ment. (c) Dose-dependent effects on cytokine production in non-human primates. Only very high dosage led to significant increases in cytokines, (a, b) reprinted with permission from [174], figures 3 and 5. 2005 American Association for Cancer Research, (c) reprinted with permission from [177]. 2007 National Academy of Sciences, U.S.A...

The complex multicomponent system, called CALAA-01, has been developed by Davis for Calando Pharmaceuticals and is the first of many possible RONDEL therapeutics based on a biomimetic approach to drug delivery [24], The approach combines a linear cationic polymer that incorporates cyclodextrins, a therapeutic payload (siRNA strands that target a specific process), and adamantane molecules modified with biocompatible polyethylene glycol chains (PEGs) or complementary proteins that bind to the target cell types. 

Cholesterol is absorbed by intestinal epithelial cells via a Niemann-Pick Cl-Like 1 (NPCILI) protein. This is the target of a number of anti-hyperhpidaemic drugs used to lower cholesterol levels. Examples include miglustafi aUopregnanolone, oxysterols and cyclodextrins all are able to slow the progress of the disease, but none as yet provides an... 

Schaschke N, Assfatglvlachleidt I, Machleidt W, et al. P-Cyclodextrin/epoxysuccinyl peptide conjugates a new drag targeting system for tumor cells. Bioorg Med Chem Lett 2000 10 677-680. 

The crucial challenge of in vivo application of RNAi therapy is developing efficient delivery system to transport the siRNA into the tissue and finally into the cytoplasm or shRNA into the nucleus of target cells [4]. Several studies have demonstrated efficient delivery of siRNA in vivo as well as its therapeutic effect in animal model. Recently in 2008, FDA approved the first clinical study using targeted cyclodextrin-containing nanoparticle for the systemic delivery of an anti-cancer siRNA, RONDEL , developed by Calando Pharmaceutical Inc. 

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