Biodegradable polyrotaxanes

In the last few years there have been new creative methods of preparation of novel hydrophilic polymers and hydrogels that may represent the future in drug delivery applications. The focus in these studies has been the development of polymeric structures with precise molecular architectures. Stupp et al. (1997) synthesized self-assembled triblock copolymer, nanostructures that may have very promising applications in controlled drug delivery. Novel biodegradable polymers, such as polyrotaxanes, have been developed that have particularly exciting molecular assemblies for drug delivery (Ooya and Yui, 1997). 

The aqueous solubility of CD also enables their potential application as poly-rotaxane-based drug carriers. Yui and coworkers incorporated CD onto PEO chains in polypseudorotaxanes and polyrotaxanes [92-94], The releasing kinetics of CD from the polymer chain were studied. The release was governed by the inclusion complexation equilibrium. Biodegradation to cleave the BG units was shown to cause the release of the CD from the polyrotaxanes. 

Supramolecular dissociation of the polyrotaxanes into constituent molecules such as a-CD and PEG was quite a new image as a mode of biodegradation in a living body. This insight was the first step to initiate our studies on polyrotaxanes as biomaterials 15 years ago [6],... 

Yui s group has investigated biodegradable polymers based on the cyclodextrin-based polyrotaxanes over the course of the last decade [128-139]. First, they prepared polyrotaxanes from a-cyclodextrin and PEG bisamine (Scheme 23) [128]. For example, l-phenylalanine was employed as an enzymatically hydrolyzable endcap. The in vitro degradation experiments using papain showed that a-cyclo dextrin was indeed released only when the terminal peptide linkages were hydrolyzed. They have prepared various kinds of polyrotaxanes based on cyclodextrin and have demonstrated that these polyrotaxanes are effective as drug delivery systems. 

Yui s group found the thermal stability of their biodegradable polyrotaxane was better than that of the separate components, poly( -lysine) and a-cyclodextrin [12,13]. In some crown ether based systems, as shown below, thermal stabihty decreases because of the lability of the cyclic components. 

T. Ooya and N. Yui, Synthesis and characterization of biodegradable polyrotaxane as a novel supramolecular-structured drug carrier,/. Biomat. Sci. -Polym. E., 8,437-455 (1997). 

Yui et al. also developed biodegradable hydrogels cross-linked by topological bonds. Polyrotaxanes consisting of... 

Drug-Conjugated Biodegradable Cyclodextrin-Based Polyrotaxane... 

Fig. 13 The biodegradable polyrotaxane systems based on HP-modified a-CD and PEO. a The structure of the HP-conjugated polyrotaxane systems b HP-a-CD release by terminal peptide cleavage of HP-a-CD/PEO-Phe system...

The biodegradable HP-a-CDs/PEO polyrotaxane could also be useful in the fabrication of blood-contacting devices based on the intracellular metabolism of platelets and physiochemical interaction of the polyrotaxanes with the plasma membrane. For instance, based on a cellular response study, HP-a-CDs/PEO... 

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