Doxorubicin loaded GM1 ganglioside nanomicelles for targetted delivery of anticancer drugs: Characterization and evaluation of their in vitro cytotoxicity

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

Ciudad de Buenos Aires - Argentina

Congreso; Nanomercosur 2013. Nanotecnología para la competitividad industrial; 2013

When dissolved in water, GM1 monosialoganglioside spontaneously self-aggregate forming micelles. We demonstrate herein that Doxorubicine (DOX), an anthracycline anticancer drug with high water solubility, can be successfully incorporated into GM1 ganglioside micelles through a process that is essentially independent of the concentration of NaCl indicating that the association involves mostly 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 incorporation of DOX into GM1 micelles was observed over a broad range of temperature (4 - 55 ºC). 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. Diffusion 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.