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1Laboratoire de Chimie des Polymères Organiques - Pessac - France

CNRS UMR5629 - Université Bordeaux 1- Institut Polytechnique de Bordeaux 2Department of Chemical Engineering, Waterloo Institute of Nanotechnology,

University of Waterloo, Waterloo, Canada

INTRODUCTION – Drug delivery system

•Correspondants: lecommandoux@enscbp.fr, mkctam@uwaterloo.ca Acknowledgements: Université Bordeaux 1, Conseil régional d’Aquitaine, IDS-FunMat, IPB-ENSBP for their financial support

•Ring opening polymerisation •Organic N-Heterocyclic carbene catalyst eliminates traditional meta l catalysts and metallic by products •Good control,accurate targeting of DPs

• Functionalisation of PTMC block via UV-initiated thiol-ene “click” chemistry •Fast reaction time, ambient conditions

• Ring opening polymerisation utilizing a macromolecular initiator

PTMC

DPtarget DPExpt PDI

13 12 1.07

30 29 1.09

50 46 1.05

Functionalized PTMC

CHCl2, 48 h

TFA/HBr

Via Nanoprecipitation

Model Chemistry

Enzyme-Responsive Trigger (In Progress) • In the presence of MMP enzymes, peptide is cleaved and drug released

MMP 2, 9 •Synthetic peptide can be specifically cleaved by MMP 2, 9 enzymes found almost exclusively in tumour microenvironments

A - P - V - G - L - I - G - A - C

• Macromolecular coupling via thiol-ene “click” chemistry •Optimal conditions under review

•Ring opening polymerisation utilizing a macromolecular initiator

Procaine Selective Electrode

Electrode Validation

~200 nm

• Traditional methods of drug quantification suffer from a number of inaccuracies • Drug-selective membranes can be synthesized and used for direct electro-chemical measurements of drug concentrations

Future Work

• Current cancer therapies suffer from a lack of specificity •Therapeutics damage both diseased and healthy cells •Aim to exploit the unique enzymatic environment of tumour cells for a targeted and triggered delivery system •Polymersomes based on PTMC-b-PGA coploymer

a) Schematic of double barrier effect. b) changes in drug release profiles due to changes in dialysis bag MWCO

•Quantifying drug release by dialysis suffers from double-barrier effect and inaccuracies due to dialysis membrane interference

Procaine-Selective Membrane

Drug/PVC Plasticizer NaTPS

50 % 49 % 1 %

y = 12.706ln(x) + 181.63 R² = 0.9857

50

100

150

0.0004 0.04

Vo

ltag

e (m

V)

Procaine Concentration (mol/L)

Quantifying drug concentrations

a) Electrode response over a range of concentrations. b) Electrode response over 24 h.

• Live monitoring of drug loading and release from polymersomes using drug-selective electrodes •Development of electrodes responsive to various other drugs

•Assembly of polymersomes from PTMC-peptide-PGA system and loading of drugs •Measurements of burst release in the presence of MMP-2,9

Daniel Bacinello1, 2, Michael Tam2, Daniel Taton1, Sébastien Lecommandoux1

LCPO

a) Schematic of electrode b) Schematic of electro-

chemical cell

a b c

a b

0

50

100

150

0.0 10.0 20.0 30.0

Vo

ltag

e (m

V)

Time (h)

c) Procaine-selective membrane composition

•Probe shows logarithmic response over a range of drug concentrations and drift of 0.3 mV/h over a 24 h period

a b IPR 20

12