3rd Long-Acting Injectables and Implantables Conference, February 6th 2020, San Diego, USA

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 722717.

HYDROGELS FOR PROTEIN DELIVERYWim E. Hennink, Blessing C. Ilochonwu, Carl Schuurmans, Tina Vermonden

Why hydrogels for release of proteins?

BiocompatibilityDegradability/selection of building blockPossibilities to tailor releases (water content/crosslink density/degradation kinetics)Different geometries (macroscopic/microspheres/nanoparticles)

Crosslinking might affect protein stability/integrityapproach: post loading; protein friendly crosslinking chemistry

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Complex coacervation-based protein loading and tunable release from monodisperse glycosaminoglycan

microgels

Complex coacervates

3. Van der Gucht et al. Journal of Colloid and Interface Science 2011

Charged materials - Hypothesis

Polymer Mn in kDa

PDI DM in %

HAMA 57 nd. 12.6

CSMA 27 (94wt%)354 (6 wt%)

1.41.3

11.8

HAMA (-1 per monomer) /CSMA (-2 per monomer)

3.

Lysozyme:128 residues14.3 kDa+8 charge (pH 7.4)

Preparation of monodisperse HA/CS microgels

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Fabrication of HAMA and CSMA microgels

0 1 2 3 4 5 6 7 80

1 0

2 0

3 0

4 0

5 0

C o n tin u o u s f lo w ra te (m L /m in )C

oV

(%

)

Scale bar = 500 µm

4.

0 1 2 3 4 5 6 7 80

1 0 0

2 0 0

3 0 0

4 0 0

5 0 0

6 0 0

C o n tin u o u s f lo w ra te (m L /m in )

Dro

ple

t d

iam

ete

r (µ

m) 5 w t% C S M A (a q )

2 .5 w t% H A M A (a q )

5 w t% H A M A (a q )

A .

Soft Matter, 2018,14, 6327-6341

Loading of CS/HA microgels with lysozyme in low ionic strength buffer of pH 7.4

Results: Quantitative loadingHigh loading capacity (3-4 mg protein per 1 mg HA/CS)Deswelling of the microspheres

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Lysozyme release from microgels

8.

HAMA ( 1 COO-) CSMA (1 COO- and 1 SO4-)

Lysozyme release from CSMA microgels in scaffolds

9.

0 5 1 0 1 5 2 0 2 5 3 00

2 0

4 0

6 0

8 0

1 0 0

T im e (d a y s )

Cu

mu

lati

ve

re

lea

se

(%

)

5 0 0 m M

E .

0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 5 0 5 5 6 00

2 0

4 0

6 0

8 0

1 0 0

T im e (d a y s )

Cu

mu

lati

ve

re

lea

se

(%

)

1 7 0 m M

D .

Soft Matter, 2018,14, 6327-6341

2.

Polymer Mn in kDa

PDI DM in %

HAMA 57 nd. 12.6

CSMA 27 (94wt%)354 (6 wt%)

1.41.3

11.8

Thermopolymer

35 2.0 9.5 – 10.1

Thermopolymer

Release from scaffolds

methacrylated poly[N-2hydroxypropyl)methacrylamidemono/dilactate]-PEG triblock co-polymer

2.

Release from scaffolds

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