Reduction the Initial-Burst Release of Doxorubicin from Polymeric Depot as a Local Drug Delivery System for Cancer Treatment.

A sustained release that can be controllable is an ultimate goal for the delivery of drugs in drug delivery systems including in situ depots. However, one of the major persistent problems in the controlled release delivery system development is the initial burst release of the loaded drug which can minimize the effectiveness of the system. Our primary research objective was to reduce the initial burst release of Doxorubicin (Dox) encapsulated in polymeric depots by incorporating deprotonated Dox into the depots. The drug release profile and cytotoxicity effect of various concentrations of hydrophobic Dox-loaded depots were studied. In the first 24 hours after forming the depots, the release of Dox reached 82.9 ± 0.6% in Dox·HCl depots. Interestingly, the initial burst releases of 5, 10 and 15% wt/wt hydrophobic Dox-loaded PLEC depots were reduced to 48.5 ± 10.0, 29.2 ± 7.8 and 18.9 ± 0.9%, respectively. Moreover, 15% hydrophobic Dox-loaded PLEC depots maintained their stability up to 14 days and their in vitro cytotoxicity ability against human hepatocellular carcinoma cell line (HepG2). Taken together, this study suggested that the presence of hydrophobic Dox in Dox-loaded PLEC depots reduced the initial burst release phenomenon of the drug and the depots still maintained their function as a local drug delivery system.