Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery...

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Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center [email protected]

Transcript of Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery...

Page 1: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Electrospun nanofibers at University of Helsinki

Dr. Antti Laukkanen

8.2.2007

DDTC

Drug Discovery and Development Technology Center

[email protected]

Page 2: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Cell Culture Models

On filter, for example Toropainen et al.:

Culture model of human corneal epithelium for prediction of

ocular drug absorption

Toropainen E, Ranta VP, Talvitie A, Suhonen P, Urtti A: Invest Ophthalmol Vis Sci., 2001, 42, 2942-2948.

More difficult with other cell types which need truly 3D

environment

Page 3: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Extra Cellular Matrix – Should we try to mimic it?

Griffith L. and Swartz M., Nature Reviews, 216 (7), 2006

Page 4: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Advanced matrices

Schematic drawing of an artificial mimic of an extracellular matrix. The fibrillar skeleton is composed of electrospun biodegradable polymer fibers. The matrix is modified by incorporating cell adhesion ligands on the surface of nanofibers to improve the cell attachment. Hydrophilicity is increased with grafted polymer chains and the cell culturing is controlled with a controlled release of growth factors.

Page 5: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Advanced matrices

1. Electrospinning of functional polymers

2. Post-modification with peptides or direct solid phase

synthesis

Page 6: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Functional polymers and functional fibers

What is the needed functionality? Fiber should be cross-linkable or water insoluble

, UV, or plasma treatment What other solvents should be tolerated?

OH

Cl

NH

NH2

OH

Page 7: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Fibers for solid phase synthesis

Need for highly stable amino functionalized polymer Should tolerate DMF and NMP

Cl Cl

NH2

NH2

NH

NH2

+Toluene, 35 - 70 °C48 h + 2 h

Toluene60 °C

AIBN

Synthesis route of amino-functional poly(styrene). The amino-modification could be conducted before or after the electrospinning.

The role 1,4 diaminobutane is twofold: first it will provide the needed amino-functionality on the fibers and secondly it will slightly cross-link the nanofibers. The degree of cross-linking is dependent on the relative amounts of diamine and chloromethyl functionality in the modification reaction.

Page 8: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Electrospinning Instrumentation

V

Polymer solution

Needle

High voltage power supply

Collector

+++

++

+++

Taylor cone Simplified set-up

Page 9: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

The Electrospinning device

Page 10: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

Pore size 20-30 m

PVP Nanofibers

Page 11: Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi.

PEVA Nanofibers

Water insoluble – stable in physiological conditions Fiber diameter 1 -2 m, pore size 20-40 m Easily modified via hydroxyl group Possibility to graft other chains by redox polymerization

OH

0.27 0.73