Microbes as biosensors to monitor drug release : a calorimetric approach

The release of the anticancer drug doxorubicin (DOX) incorporated in a new drug carrier, namely a Liposomal Locked-in Dendrimer (LLD)1 formed by DPPC-DPPG phospholipids and the PAMAM 3,5 dendrimer, was studied by means of isothermal titration calorimetry (ITC) following the influence of the drug on the growth kinetics of the Lactobacillus helveticus. This microbe is a homofermentative thermophilic lactic acid bacterium (LAB), extensively used in food fermentation, and is a “Generally Recognised as Safe” (GRAS) organism. The bacterial growth was followed alone and in the presence of LLDs 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). Classical microbiological investigations were also performed in parallel. The results allow suggestion of models that may quantitatively relate the microbial growth with the drug concentration that depends on the release rate from the LLD. Such models have a general validity and may be applied to a number of similar situations.