The recovery method influences properties of adenosine derivatives loaded nanospheres

Purpose: The aim of this study was to evaluate the proprieties (size, drug loading, drug release and drug stability in human whole blood) of poly(lactic acid) nanoparticles embedded with an adenosine derivative (pro-drug 5' octanoil cyclopentyladenosine having antiischemic activity) as a function of both the stabilizing agent used in the preparation and the recovery method. Methods: Nanoparticles were prepared by nanoprecipitation method in the presence of Pluronic F68 or Sodium Cholate as stabilizing agents. The nanoparticles were recovered by gel-filtration or ultracentrifugation or dialysis and, than, freeze-dried. Results: In the presence of Sodium Cholate very small nanoparticles were obtained (mean size of 110 ± 20 nm) whereas in the presence of Pluronic F68 the mean size was of 250 ± 50 nm. Independent from the recovery method, the smallest nanoparticles, obtained in the presence of Sodium Cholate, displayed a good drug loading but a very fast drug release rate. On the contrary, as concern nanoparticles obtained in the presence of Pluronic F68, the recovery procedure strongly influences the drug loading and release. The sample recovered by gel-filtration showed a satisfactory control in the drug release although revealed a low drug loading. Moreover, the encapsulation of the pro-drug in the samples recovered by gel-filtration or by ultracentrifugation allows respectively to increase the half life of the drug form 30 to 90 min or strongly stabilize the 15% of the loaded drug amount. Conclusion: The results suggest that the stabilizing agent appreciably affects the nanoparticle size. For the larger particle, the recovery procedures affect drug loading, drug release and, thus, in vitro drug stability. Further investigation will be carried out in order to confirm in vivo the increase in the drug stability observed in human whole blood