Active Agents to Hyaluronan

We previously described chemical modification approaches that have been used to derivatize HA (36). This section focuses on recent literature reports on conjugation of active moieties to HA. Several earlier articles dealing with this topic have been published elsewhere (37-42). 

Similarly, modified HA bearing hydrazide and aldehyde functionalities that cross-link upon mixing was used as a vehicle for bupivacaine (49). A 2% (w/v) cross-linked HA doubled the duration of block in a rat sciatic nerve blockade model, without a statistically significant increase in myotoxicity. 

The opioid drugs morphine and codeine as well as the analog naloxone were conjugated to HA via two types of hydrolytically labile ester bonds and drug release kinetics from these conjugates were systematically investigated (50). 

Although paclitaxel (PTX) has shown tremendous potential as an anticancer drug, its utility has been compromised by its poor aqueous solubility. PTX conjugation to HA was carried out to increase water solubility and potentially target it toward cells that overexpress HA cell surface receptors (e.g., CD44). 

One conjugation approach exploited the higher nucleophiUcity of acyl hydra-zides compared to amines during EDC-mediated couplings (39,51,52). This use of difunctional dihydrazides has also been reported to allow facile access to other HA conjugates (Fig. 2). 

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