Purpose The aim is to provide a proof of concept on the possible use of Sertoli cells (SC) as potential drug carriers. This idea arises from the phagocytic and immune competence of SC, which, in addition, have been found to distribute to the perialveolar area when injected intravenously in mice. Methods An ofloxacin-palladium complex encapsulated into spray-dried PLA microspheres (MS), previously developed, was used as a model system to be loaded into SC. The MS were characterized in terms of morphology, drug content and release. SC were incubated in HAM-F12 medium at 37°C in 5% CO2 with a dispersion of MS and phagocytosis was monitored over 0-24 hours. The uptake was measured by HPLC at determined time points and followed over 6 days. SC viability and morphology were assessed accordingly. Reactive oxygen species (ROS) and DNA damage were also evaluated over time. Moreover, the SC loaded with MS were characterized after being frozen at -80°C and followed up over 6 days. Uptake, ROS and DNA damage were assayed again. Results SC successfully internalized drug loaded MS with an uptake around 20% at 5 hours that increased to 30% until day two. The drug content in SC remained constant up to 6 days and viability was maintained over time as well. ROS and DNA damage assays showed low expressions with no particular differences between controls and treated SC at all time points. These results were confirmed even upon freezing of the treated SC with the exception of the SC at day 6 that showed a slight increase in ROS. However, the treated SC were viable and capable of maintaining the amount of drug in the cell constant throughout the experiment. Such data were confirmed by morphological evaluations. Conclusion SC were able of a high phagocytic performance and to bear a high load of drug loaded MS over time. Freezing seemed to be possible in order to store cells over a long period of time. Even though only preliminary, these results encourage further studies to finalize the potential use of SC as drug delivery vehicles.
Sertoli Cells as potential drug carriers: uptake and stability
GIOVAGNOLI, Stefano;LUCA, Giovanni;MANCUSO, FRANCESCA;CALVITTI, Mario;SCHOUBBEN, Aurelie Marie Madeleine;BLASI, PAOLO;GALLI, Francesco;MORETTI, Massimo;BECCHETTI, Ennio;RICCI, Maurizio;CALAFIORE, Riccardo
2012
Abstract
Purpose The aim is to provide a proof of concept on the possible use of Sertoli cells (SC) as potential drug carriers. This idea arises from the phagocytic and immune competence of SC, which, in addition, have been found to distribute to the perialveolar area when injected intravenously in mice. Methods An ofloxacin-palladium complex encapsulated into spray-dried PLA microspheres (MS), previously developed, was used as a model system to be loaded into SC. The MS were characterized in terms of morphology, drug content and release. SC were incubated in HAM-F12 medium at 37°C in 5% CO2 with a dispersion of MS and phagocytosis was monitored over 0-24 hours. The uptake was measured by HPLC at determined time points and followed over 6 days. SC viability and morphology were assessed accordingly. Reactive oxygen species (ROS) and DNA damage were also evaluated over time. Moreover, the SC loaded with MS were characterized after being frozen at -80°C and followed up over 6 days. Uptake, ROS and DNA damage were assayed again. Results SC successfully internalized drug loaded MS with an uptake around 20% at 5 hours that increased to 30% until day two. The drug content in SC remained constant up to 6 days and viability was maintained over time as well. ROS and DNA damage assays showed low expressions with no particular differences between controls and treated SC at all time points. These results were confirmed even upon freezing of the treated SC with the exception of the SC at day 6 that showed a slight increase in ROS. However, the treated SC were viable and capable of maintaining the amount of drug in the cell constant throughout the experiment. Such data were confirmed by morphological evaluations. Conclusion SC were able of a high phagocytic performance and to bear a high load of drug loaded MS over time. Freezing seemed to be possible in order to store cells over a long period of time. Even though only preliminary, these results encourage further studies to finalize the potential use of SC as drug delivery vehicles.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
