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

Authors
Cuestas, María Luján; Glisoni, Romina Julieta; Mathet, Veronica Lidia; Sosnik, Alejandro Dario
Publication Year
2013
Language
English
Format
article
Status
Published version
Description
Aiming to develop polymeric self-assembly nanocarriers with potential applications in active drug targeting to the liver, linear and branched poly(ethylene oxide)- poly(propylene oxide) (PEO-PPO) amphiphiles were conjugated to lactobionic acid (LA), a disaccharide of galactose and gluconic acid, by the conventional Steglich esterification reaction. The conjugation was confirmed by ATR/FT-IR, 1H-NMR and 13C-NMR spectroscopy. MALDI-TOF mass spectrometry and elemental analysis were employed to elucidate the conjugation extent and the final molecular weight, respectively. The critical micellar concentration (CMC), the size and size distribution and zeta potential of the pristine and modified polymeric micelles under different conditions of pH and temperature were characterized by dynamic light scattering (DLS). Conjugation with LA favored the micellization process, leading to a decrease of the CMC with respect to the pristine counterpart, this phenomenon being independent of the pH and the temperature. At 37ºC, micelles made of pristine copolymers showed a monomodal size distribution between 12.8 and 24.4 nm. Conversely, LA-conjugated micelles showed a bimodal size pattern that comprised a main fraction of relatively small size (11.6-22.2 nm) and a second one with remarkably larger sizes of up to 941.4 nm. The former corresponded to single micelles, while the latter would indicate a secondary aggregation phenomenon. The spherical morphology of LA-micelles was visualized by transmission electron microscopy. Finally, to assess the ability of the LAconjugated micelles to interact with lectin-like receptors, samples were incubated with concanavalin A at 37ºC and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this vegetal lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site in the lectin with the gluconic acid unit of LA.
Fil: Cuestas, María Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;
Fil: Glisoni, Romina Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;
Fil: Mathet, Veronica Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;
Fil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;
Subject
Poly(ethylene oxide)-poly(propylene oxide) polymeric micelles
Lactobionic acid-conjugated poloxamers and poloxamines
Steglich esterification
Lectin-like receptors
Concanavalin A agglutination
Bioquímica y Biología Molecular
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Nano-materiales
Nanotecnología
INGENIERÍAS Y TECNOLOGÍAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/1762