Polymer Encapsulated siRNA Delivery

The first example of a bionanopharmaceutical that exemplifies the range of supramolecular chemical motifs that can be harnessed to deliver drugs in 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. 

The importance of this approach to drug delivery is that it is modular so that variations can be made to each component. Thus the adamantane substituents can be varied to elicit different biological responses or bind to other protein receptors. The polymer can be varied so that it binds to different guest molecules, incorporates different macrocycles or unravels under different conditions. Finally, and most importantly, the guest can be varied from the large, charged siRNAs down to small drug molecules. 

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Tremendous efforts have been made to overcome these challenges, cationic liposome and positively charged polymers are currently being used as the most common method to complex with negatively charged siRNA for systemic delivery [30, 36]. Other in vivo delivery approaches include conjugation with cholesterol, aptamer, peptide complexation with antibody-protamine fusion protein or encapsulation in cyclodextrin nanoparticles [35, 37-39]. 

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