Abstract
A new concept for inflammation responsive drug delivery systems using biodegradable hydrogels of crosslinked hyaluronic acid (HA) has been proposed in our recent studies [ l-3 1. HA is well known to be degraded specifically b;r the presence of hydroxyl radicals, which are produced by phagocytic cells such as leukocytes and macrophages, locally at inflammatory sites [ 41. Our system was established by constructing a heterogeneous-structured device of drug microreservoirs (lipid microspheres) dispersed into degradable matrices of crosslinked HA gels. The most attractive characteristics of this device are: (1) to release lipid microspheres (LM) in response to surface-controlled degradation of crosslinked HA gels and (2) to be quantitatively inflammation-responsive and degradable. These unique features of the device are favorable to regulate drug delivery in several inflammatoryrelated diseases, where LM are released in response to inflammation-induced degradation. The heterogeneous structured device of our design has much potential in drug delivery for severe inflammation. It is well recognized that dysfunction induced by free radicals may be a
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