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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: [email protected], [email protected] 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
