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A01-01 Radiation synthesis of polymer nanogels for biomedical applications

Piotr Ulański, Sławomir Kadłubowski, Janusz M. Rosiak Institute of Applied Radiation Chemistry, Lodz University of Technology, Poland

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Radiation cross-linking of polymers

Improved:

Mechanical properties

Chemical resistance

Thermal resistance

New properties:

Elasticity

Memory effects

Equilibrium swelling

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Radiation cross-linking of polymers

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Radiation cross-linking of polymers in water - synthesis of hydrogels

Hydrogel wound dressings

Excellent healing properties

On the market since > 20 years

Standard burn dressing for US Marines

Very important role of IAEA in developing,

promoting and disseminating this

technology to many countries

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Intramolecular cross-linking of polymers

Ulanski et al. Radiat. Phys. Chem. 52 (1998), 289.

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Intramolecular cross-linking of polymers

A. Dybala Thesis (1997) LUT, Lodz, Poland

Ulanski et al., RPC 46 (1995), 917 Also: Works of Sabharwal et al.

PEO, N2O, pulsed EB

PVP, Ar, gamma

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Nanogels

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Idea of gene therapy based on virus as a DNA-carrying vector

Vinogradov et al., Advanced Drug Delivery Reviews 54 (2002) ,135 Current Pharmaceutical Design 12 (2006), 4703

Nanogels as carriers for gene therapy

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Kabanov & Vinogradov Angew. Chem. Int. Ed. 48 (2009), 5418

Nanogels as carriers for controlled drug delivery

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High polymer

concentration;

low dose rate

Less than one

radical per chain

Intermolecular crosslinking

a)

Low polymer

concentration;

high-dose pulse

Many radicals

per chain

Intramolecular crosslinking

b)

Preparative Pulse Radiolysis

Kadłubowski et al., Macromolecules 36 (2003), 2484. Kadłubowski, RPC 102 (2014), 29.

How to achieve intramolecular cross-linking ?

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Excellent developments & achievements:

Palermo (prof. Dispenza)

Maryland (prof. Al-Sheikhly)

Ankara (prof. Güven)

Dresden (prof. Arndt)

And many other labs worldwide

Radiation synthesis of nanogels

Tested & proven to be quite universal:

Typical water-soluble polymers

Polyelectrolytes, temperature-sensitive polymers

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Two-step method - independently chosen size and weight

0 2

0.0

0.5

1.0

1.5

Rg

Mw

intramolecular

crosslinking

intermolecular

crosslinking

high dose ratelow dose rate

Dose / a.u.

Mw

/ a

.u.

0.0

0.5

1.0

1.5

Rg

/ a.u

.

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0 100 1000 100001

10

40

Mw / M

Da

Dawka / Gy

gamma

0,42 Gy s-1

400 mM

EB

0,9 kGy/pulse

15 mM

PVP

0 100 1000 1000020

100

700

Rg / n

m

Dawka / Gy

PVP

Dose / Gy Dose / Gy

Kadłubowski et al., Polymer 53 (2012), 1985

Two-step method - independently chosen size and weight

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MC simulation - Cooperative Motion Algorithm (CMA)

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2

3

4

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Trace of previous chain locations

New chain location

Radicals that haven’t yet reacted

Segments joined by a crosslink formed upon recombination of two radicals

End-to-end distance J.K. Jeszka, S. Kadłubowski, P. Ulański, Macromolecules 39 (2006), 857.

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+ C

O

OH

N+

O

N

NN

OO

S OO

O

CH3

C

O

O

N

NN

OO

C

O

O

N

NN

OO

+

NH2

NH2

C

O

NH NH2

NH2

NHNH

NH2

Q G K L W N Q G A V M H L K

DOTA

NH2

NH2

NH2

NH2

NHNH

NH2

Q G K L W N Q G A V M H L K

DOTA

Nanogels for targeted radiotherapy

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Providing means to develop infrastructure, for trainings, dissemination

of knowledge and skills (TC Projects)

Stimulating and promoting international cooperation (Consultant

Meetings, Regional Courses, Coordinated Research Projects)

Nanoscale Radiation Engineering of Advanced Materials for Potential

Biomedical Applications, F23028 (2009-2013)

Instructive Surfaces and Scaffolds for Tissue Engineering Using Radiation

Technology, F23030 (2014-2019)

Nanosized Delivery Systems for Radiopharmaceuticals, F22064 (2014-2019)

Special thanks – Olgun Güven, Andrzej Chmielewski, Mohammad

Haji-Saeid, Sunil Sabharwal, Meera Venkatesh, Agnes Safrany

Decisive input of the IAEA

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International Atomic Energy Agency

- CRPs

National Science Centre (Poland)

– OPUS (UMO-2012/07/B/ST4/01429)

National Centre for Research

and Development (Poland)

– DERMOSTIM, POLYCELL

Ministry of Science and Higher

Education (Poland)

- supporting student exchange

Sponsors (most recent works)

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THANK YOU !