Proposed molecular model for electrostatic interactions between insulin and chitosan. Nano-complexation and activity in cultured cells

CECILIA PRUDKIN-SILVA; KARINA MARTINEZ; MARÍA EDITH FARÍAS; FEDERICO COLUCCIO- LESKOW; OSCAR PÉREZ

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017

0141-8130

The objective of this contribution was to propose amodel that would explain the nanocomplexes formation between Human RecombinantInsulin (I) and a polydisperse Chitosan (CS). Such an objective impliedexploring I and CS concentration conditions that allowed the formation ofcomplexes with defined and reproducible submicronic dimensions. I-CS complexes wereobtained by mixing I and CS solutions at pH 2 and then increasing the pH up to6 promoting electrostatic interactions between them. Colloidal stages of I andI-CS nano-complexes formation were characterized by dynamic light scattering (DLS), ζ-potential, solutions flow behavior and absorbancemeasurements. 1·10-2%, w/w, of CS allowed covering completely thesurface protein aggregates constituting core?shell nano-structures of 200 nm, with a ζ-potential of 17,5 mV. Solution dynamic viscosity results keptrelation with different stages of nano-complexation process. Biologicalactivity of I-CS complexes was studied in 3T3-L1 cultured fibroblast showing adelayed and sustained activity as compared to free insulin. I-CS nano-complexes could be an alternative fordeveloping a new generation of drugs allowing I protection from the hostileconditions of the body and increasing its absorption. These findings have basicand practical impacts as they could be exploited to exert the controlledrelease of I in therapeutic formulations by using the I-CS nano-complexes.