Self-assembled ganglioside nanomicelles for dosorubicin delivery: characterization and evaluation of their in-vitro cytotoxicity

LEONHARD V; ALASINO RV; BIANCO ID; GARRO AG; HEREDIA V; BELTRAMO DM

Congreso; III Reunión Nanocordoba 2014; 2014

We demonstrate herein that self-assembled GM1 micelles are able to spontaneously load an anthracycline anticancer drug with high water solubility as Doxorubicine (DOX) through a process that mostly involves hydrophobic interactions. A substantial drug loading level was achieved after incubation of DOX with the micelles at 4 oC during 24 h. With 50 mg.mL-1 of GM1 a saturating level of 10 mg.mL-1 DOX was attained, which is five times greater than the concentration in liposomal commercial products. The drug-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4 - 25 oC. Di↵usion of GM1 from the micelles was restricted upon mixed-micelles formation with a displacement or the equilibrium towards micelles indicating that GM1/DOX micelles are kinetically and thermodynamically more stable than pure GM1 micelles. Upon exposure to blood components it was observed that GM1/DOX micelles interact with human serum albumin (HSA). However, the amount of HSA that ended associated to the micelles was inversely related to the amount of DOX suggesting that both could share their binding sites. The results of in-vitro assays showed that the antimitotic activity of these GM1/DOX micelles was quantitatively equivalent to that of the free drug in solution indicating that its incorporation into GM1 micelles did not impair its activity