Objective The aim of this work was to investigate the stability of lipid nanoparticles (NPs) upon dilution in different media and temperatures. This kind of investigation is overlooked in literature even though very important. In fact, in order to assess the real potential of colloidal carriers in drug delivery, aggregation phenomena should be known and, if possible, avoided. Experimental Polysorbate 80 (P80) and poloxamer 338 (P338) stabilized cetylpalmitate (CP) NPs were prepared using the hot high pressure homogenization technique. Particle sizes were determined with photon correlation spectroscopy, using a Nicomp 380 autocorrelator equipped with a Coherent Innova 70-3 argon ion laser. Lipid NPs dimensions were expressed as mean hydrodynamic diameter (MHD) and Gaussian distribution width (GDW). The suspensions were diluted 50, 100, 250, and 500 times with cell culture medium F12 without FCS or alternatively physiological solution and stored at 4 or 37°C. CP NPs were monitored for 7 days in cell culture media and 21 days in physiological solution. Results Lipid NPs were successfully produced and characterized by dimensions suitable for parenteral administration. P80 and P338 stabilized NPs showed a MHD around 180 nm and a GDW of 50 and 70 nm, respectively. Upon dilution with liquid culture broth, both suspensions were stable for 7 days at 4 and 37°C. Dilution did not affect the MHD nor the GDW, except for P80 stabilized NPs diluted 500 times and maintained at 37°C. In this case, aggregation was evident already after 24 hours. Upon dilution with physiological solution, P338 CP NPs were stable for 21 days at all dilutions and temperatures. In the case of P80 lipid NPs, the MHD and GDW values did not increased for 21 days at both temperatures only when the suspension was not diluted. After 21 days at 4°C, the MHD was 30 nm larger for all dilutions. The situation worsened at 37°C. In the worst case (dilution 500 folds), both MHD and GDW were higher already after 24 hours and, after 21 days, MHD and GDW were 80 nm and 140 nm higher, respectively. Conclusions NPs stabilized with P80 and P338 were stable for 7 days when diluted up to 500 times at both 4 and 37°C. After 21 days, similar results were obtained for P338 stabilized NPs diluted with physiological solution. On the contrary, P80 stabilized NPs, when diluted with physiological solution, showed some aggregation after 24 hours at 37°C and after 21 days at 4°C.
Stability of lipid nanoparticles in physiological relevant media.
BLASI, PAOLO;SCHOUBBEN, Aurelie Marie Madeleine;RICCI, Maurizio
2012
Abstract
Objective The aim of this work was to investigate the stability of lipid nanoparticles (NPs) upon dilution in different media and temperatures. This kind of investigation is overlooked in literature even though very important. In fact, in order to assess the real potential of colloidal carriers in drug delivery, aggregation phenomena should be known and, if possible, avoided. Experimental Polysorbate 80 (P80) and poloxamer 338 (P338) stabilized cetylpalmitate (CP) NPs were prepared using the hot high pressure homogenization technique. Particle sizes were determined with photon correlation spectroscopy, using a Nicomp 380 autocorrelator equipped with a Coherent Innova 70-3 argon ion laser. Lipid NPs dimensions were expressed as mean hydrodynamic diameter (MHD) and Gaussian distribution width (GDW). The suspensions were diluted 50, 100, 250, and 500 times with cell culture medium F12 without FCS or alternatively physiological solution and stored at 4 or 37°C. CP NPs were monitored for 7 days in cell culture media and 21 days in physiological solution. Results Lipid NPs were successfully produced and characterized by dimensions suitable for parenteral administration. P80 and P338 stabilized NPs showed a MHD around 180 nm and a GDW of 50 and 70 nm, respectively. Upon dilution with liquid culture broth, both suspensions were stable for 7 days at 4 and 37°C. Dilution did not affect the MHD nor the GDW, except for P80 stabilized NPs diluted 500 times and maintained at 37°C. In this case, aggregation was evident already after 24 hours. Upon dilution with physiological solution, P338 CP NPs were stable for 21 days at all dilutions and temperatures. In the case of P80 lipid NPs, the MHD and GDW values did not increased for 21 days at both temperatures only when the suspension was not diluted. After 21 days at 4°C, the MHD was 30 nm larger for all dilutions. The situation worsened at 37°C. In the worst case (dilution 500 folds), both MHD and GDW were higher already after 24 hours and, after 21 days, MHD and GDW were 80 nm and 140 nm higher, respectively. Conclusions NPs stabilized with P80 and P338 were stable for 7 days when diluted up to 500 times at both 4 and 37°C. After 21 days, similar results were obtained for P338 stabilized NPs diluted with physiological solution. On the contrary, P80 stabilized NPs, when diluted with physiological solution, showed some aggregation after 24 hours at 37°C and after 21 days at 4°C.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
