Doxorubicin release from liposomal locked-in dendrimer (LLD) drug carriers : a calorimetric approach

Doxorubicin (DOX), an anticancer drug, incorporated in a new Liposomal Locked-in Dendrimer (LLD) drug carrier, formed by DPPC-DPPG phospholipids and the PAMAM 3,5 dendrimer, is released with a kinetics that can be assessed via isothermal calorimetry investigations, provided a suitable “sensor” that produces a thermal effect. In this study the selected sensor is of microbial nature, namely, Lactobacillus helveticus, which is a thermophilic lactic acid bacterium (LAB), extensively used in food fermentation, since it is a “Generally Recognised as Safe” (GRAS) organism. The release of DOX from LLD thwarts the microbial metabolism and therefore affects the intensity of the thermal effect detected. Since the calorimetric signal parallels the microbial activity, the trend observed can be quantitatively modelled and related to the kinetics of the drug release. The bacterial cultures was monitored, alone and in the presence of DOX and/or LLD, at 37 °C by means of the isothermal calorimeter DAM (Lyon, France, 10 mL volume of the measurement cell) equipped with the Microlab 500 titration system (Hamilton Company). Cell counts were also performed through standard microbiological methods. The models exploited are phenomenological and therefore may be applied to any similar system