Lactosylated poly(ethylene oxide)-poly(propylene oxide) block copolymers for potential active drug targeting: Synthesis and physicochemical and self-aggregation characterization

MARÍA L. CUESTAS, ; ROMINA J. GLISONI, ; VERÓNICA L. MATHET ; ALEJANDRO SOSNIK.

JOURNAL OF NANOPARTICLE RESEARCH

SPRINGER

Lugar: Berlin; Año: 2013 vol. 15 p. 1389 - 1409

1388-0764

Chronic hepatitis due to infection with the hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Drug targeting to liver parenchyma represents an opportunity to enhance the therapeutic outcomes in these hepatic diseases characterized by the incomplete effectiveness and the serious adverse effects of the standard drugs in non-target organs. In this study, polymeric micelles of linear and branched poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) block copolymers were surface-decorated with galactose by conjugating lactobionic acid (LA, a disaccharide of galactose and gluconic acid) to the terminal ?OH groups of the copolymer by the conventional Steglich esterification reaction. The conjugation was confirmed by ATR/FT-IR and 1H-NMR spectroscopy. MALDI-TOF mass spectrometry and elemental analysis were employed to elucidate the conjugation extent and final molecular weight and differential scanning calorimetry to characterize the thermal behavior. The critical micellar concentration, the size and size distribution and zeta potential of the pristine and modified polymeric micelles were characterized by dynamic light scattering (DLS). Conjugation with LA favored the micellization process, leading to lower CMC values. In addition, LA-conjugated micelles showed a bimodal size distribution that comprised a main fraction of relatively small size (5.0-22.2 nm) and a second one with remarkably larger sizes of up to 941.4 nm, at 37ºC. Finally, to assess the potential of these derivatives to bind lectin-like receptors, micelles were incubated with the vegetal lectin concanavalin A and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. Finally, to assess the potential of these derivatives to bind lectin-like receptors, micelles were incubated with the vegetal lectin concanavalin A and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. ?OH groups of the copolymer by the conventional Steglich esterification reaction. The conjugation was confirmed by ATR/FT-IR and 1H-NMR spectroscopy. MALDI-TOF mass spectrometry and elemental analysis were employed to elucidate the conjugation extent and final molecular weight and differential scanning calorimetry to characterize the thermal behavior. The critical micellar concentration, the size and size distribution and zeta potential of the pristine and modified polymeric micelles were characterized by dynamic light scattering (DLS). Conjugation with LA favored the micellization process, leading to lower CMC values. In addition, LA-conjugated micelles showed a bimodal size distribution that comprised a main fraction of relatively small size (5.0-22.2 nm) and a second one with remarkably larger sizes of up to 941.4 nm, at 37ºC. Finally, to assess the potential of these derivatives to bind lectin-like receptors, micelles were incubated with the vegetal lectin concanavalin A and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. Finally, to assess the potential of these derivatives to bind lectin-like receptors, micelles were incubated with the vegetal lectin concanavalin A and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. 1H-NMR spectroscopy. MALDI-TOF mass spectrometry and elemental analysis were employed to elucidate the conjugation extent and final molecular weight and differential scanning calorimetry to characterize the thermal behavior. The critical micellar concentration, the size and size distribution and zeta potential of the pristine and modified polymeric micelles were characterized by dynamic light scattering (DLS). Conjugation with LA favored the micellization process, leading to lower CMC values. In addition, LA-conjugated micelles showed a bimodal size distribution that comprised a main fraction of relatively small size (5.0-22.2 nm) and a second one with remarkably larger sizes of up to 941.4 nm, at 37ºC. Finally, to assess the potential of these derivatives to bind lectin-like receptors, micelles were incubated with the vegetal lectin concanavalin A and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. Finally, to assess the potential of these derivatives to bind lectin-like receptors, micelles were incubated with the vegetal lectin concanavalin A and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA. agglutination probably through the interaction of a secondary site with the gluconic acid unit of LA.