Biomaterials, Biodegradables and Biomimetics Research Group

Comunication - Oral

Protein nano-carriers from clicked glycosaminoglycan block copolymers


Nowadays, the treatment with conventional drugs is shifting towards therapeutic proteins that are exquisite specific and selective in executing diverse biofunctions. Glycosaminoglycans (GAGs) are natural partners of proteins in the extra cellular matrix: they stabilise and/or protect proteins from denaturation and enzymatic degradation; play a role in proteins storage or mediate their binding to specific receptors. Inspired by the native environment of proteins, we propose the use of sulfated (GAG) diblock PEG copolymers (GAG-b-PEG) for the encapsulation of proteins into nanosized interpolyelectrolyte complexes (IPECs). 


The block copolymers were synthesised following previously described procedure for hyaluronan-b-PEG.1 NMR and GPC were used to confirm the structure and molecular weight of the final products. IPECs were formed by adding a solution of poly-L-lysine (PLL) or FGF-2 in phosphate buffer pH 7.4 I=10 mM to the solution of GAG-b-PEG under vigorous stirring. IPECs were characterised by dynamic light scattering, nanoparticle tracking analysis and electron microscopy.


Oxime click reaction was used for the synthesis of diblock copolymers of polyethylene glycol (PEG) and glycosaminoglycans (GAG) with different molecular weight (Mw) and degree of sulfation (DS) (Table 1). We have tested several ratios between the PLL and the obtained copolymers. The characteristic of the PLL/GAG-b-PEG complexes at minimal zeta potential and low PDI are included in Table 1. As can be seen, IPECs with tunable size at the nanometric scale and narrow distribution were obtained.

Moreover, the size can be controlled by DS: highly sulfated GAGs form the smallest complexes that are stable to at least 500 mM ionic strength. Formation of IPECs was also achieved with a human protein FGF-2 with 98±7 nm radius and PDI 0.22±0.02 and CS12k-b-PEG.


The ability of sulphated GAG-b-PEG copolymers to carry positively charged proteins has been demonstrated by their assembly with poly-L-lysine as a model protein. The formed IPECs have neutral charge, nanometric size and stability at physiological ionic strength - properties that contribute to prolonged blood circulation times and thus, more effective delivery to the targeted site. Moreover, the complexation with basic fibroblast growth factor (FGF-2) demonstrates the feasibility of these copolymers for proteins encapsulation. These properties together with the possibility for tunable size emphasise the enormous potential of sulfated GAG-b-PEG copolymers for the engineering of delivery systems for positively charged proteins.


The authors would like to acknowledge the European European Union's Seventh Framework Programme POLARIS and NORTE-07-0124-FEDER-000016.


1. Novoa-Carballal, R.; Müller, A. H. E. Chem Commun. 48, 3781-3, 2012.

ESB 2014 - 26th European Conference on Biomaterials
FGF-2, nanobiomaterials, Sulfated GAGs
Open Access
Peer Reviewed
Year of Publication
Date Published
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