Michael KC Tam Department of Chemical Engineering University of Waterloo. Waterloo, Ontario, CANADA N2L 3G1

Transcription

1 Design of Polymeric Nanostructures for Chemical and Biomedical Applications Michael KC Tam Department of Chemical Engineering University of Waterloo 200 University Avenue West Waterloo, ntario, CANADA N2L 3G1 Revolutionary Technology Waves UW Quantum-Nano Centre 1

2 The Size of Things 1-5 nm nm Via self-assembly Macromolecules (Polymers) Human hair Via polymerization (varying MWs) Visionary in Polymer Science! In the meantime, macromolecular chemistry, too, has become a classical discipline, a mature science, with all the advantages and handicaps of maturity. Harvest is plentiful, the results are abundant but one has to ask: where is the future, where are the adventures? Quote by Helmut Ringsdorf H. Ringsdorf, B. Schlarb, J. Venzmer, Angew. Chem. Int. Ed. Engl. 1988, 27, 113. Dr. Ringsdorf promotes cross-disciplinary discussions and collaborations in the field of polymer chemistry, biology, physics and medicine 2

3 Self-assembly in Nature: (1) DNA Self-assembly in Nature: (2) Protein Source: Length of a DNA = 20,000 μm m (or 2 m) Length of a chromosome = 2 μm Slide 5 of 88 hemoglobin obin_ribbon_4subunits.jpg α-hemolysin 3

4 Self-assembly in Nature: (3) Microtubuli Self-assembly in Nature: (4) Viral capsids 4

5 Self-assemb bly in Nature e: (5) Lipids and Biomembra anes Polymers and Copolymers Polymer science, having an old tradition as an interdisciplinary field, can no longer restrict itself to common plastics. Attempts to reach new horizons have already begun. Dendrimers thers.. 5

6 RESEARCH INTERESTS SCIENTIFIC TLS Light scattering Titration calorimetry Spectroscopy(UV, FTIR) Microscopy-TEM, SEM Rheometry Physics & Thermodynamics Polymer-surfactant interactions Drug-polymer interactions Self-assembly behavior CLLABRATRS Dow Chemicals Singapore-MIT Alliance Bioprocessing Tech Inst. Colloids & Polymers RESEARCH STRATEGY & PLAN Monomers A and B N APPLICATINS Drug delivery Nano-templates Coatings & Personal care Fullerene Starting materials Hydrophobic drugs micelle ATRP/EP Synthetic Methods nucleus target cell Block copolymers, nanoogels & water-soluble fullerenes In water Delivery of drugs to targeted sites Microstructure & thermodynamics 6

7 Various Delivery Systems Plasmid DNA Block copolymer target cell Genes/DNA Simplex micelle endocytosis Protein based Drugs Protein drugs Block copolymer Simplex micelle Sinaga, A., Hatton, T.A., Tam, KC K.C., Macromolecules (2007), 40, Sinaga, A., Hatton, T.A., Tam, K.C., Biomacromolecules (2007) 8, Sinaga, A., Ravi, P., Hatton, T.A., Tam, K.C., Journal of Polymer Science Part A: Polymer Chemistry (2007), 45 (13), Peptide based block target cell endocytosis Hydrophobic Drugs Hydrophobic drugs micelle PLYMERIC DRUG DELIVERY SYSTEMS Fullerene block copolymers Wang C., Ravi, P., Tam, K.C., Langmuir (2007), copolymers 23, Ravi, P., Dai, S., Wang, C., Tam, K.C., Journal of Nanoscience and Nanotechnology (2007), 7 (4-5), Wang, C., Ravi, P., Dai, S., Tam, K.C., Langmuir (2006), 22 (17), Microgel and nanogel systems Tan, B.H., Ravi, P., Tan, L.N., Tam, K.C., Journal of Colloid & Interfacial Science (2007), 309 (2), ) Tan, J.P.K., Tam, K.C., Journal of Controlled Release (2007), 118, Tan, B.H., Ravi, P., Tam, K.C., Macromolecular Rapid Communications (2006), 27, nucleus target cell Modified Pluronic block copolymers Tian, Y., Bromberg, L., S.N. Lin, Hatton, T.A., Tam, K.C., Journal of Controlled Release (2007), 121 (3), Tian, Y., Ravi, P., Bromberg, L., Hatton, T.A., Tam, K.C., Langmuir (2007) 23, Xiong, X.Y., Li, Y., Li, Z., Zhou, C., Tam, K.C., Liu, Z., Xie, G., Journal of Controlled Release (2007), 120,

8 H n ph responsive reverse micelle N m CH 3 CH3 CH 2 C Br [CuCl]:[HMTETA]/Methanol CH 2 CH 2 Hydrolysis C CH H 3 n N n N m Low ph DMA block Hydrophobic MAA block High ph P(MAA-b-DMAEMA) Hydrophilic P(MAA-b-DMAEMA) Mao, B.W., Gan, L.H., Gan, Y.Y., Tam, K.C., Tan,.K., Polymer (2005), 46, Dai, S., Ravi P., Tam, K.C., Mao B.W., Gan L.H.,Langmuir (2003), 19, Micellization Behavior of P(DEA-b-MAA) (a) CH 2 e C ph = 12 H 2C C C H n d CH 2 CH 2 b c b H 2C N CH 2 m a a no b & c e C no a (b) ph = 12 DEA core with MAA shell ph > 9.2 f(r h ) a ph = 7 ph = 3 b ph = 3 ph < 5.5 d c e δ (ppm) R h (nm) MAA core with DEA shell 8

9 ) α-cyclodextrin Induced Assembly of PE-b-PAA at high ph α-cd PE-b-PAA Double-hydrophilic poly(ethylene oxide)-b- poly(acrylic acid) (PE-b-PAA) PAA) self-assembled into nanostructures in basic solution upon the addition of α-cyclodextrin (α-cd) CD). Self-assembly was induced by the complexation between α-cd and PE segments. Plasmid DNA interaction with PDEA-b-PE-Biotin 165 nm Aggregation Number ~ nm PDEA PE Biotin Biotin PDEA 70 -b-pe 113 M n =18,000 Da, PDI = 1.3 Plasmid DNA 37 kb B-PE-b-PDEAEMA & starting PE B-PE-b-PDEAEMA PE-b-PDEAEMA H-PE-H CH3-PE-H ζ Potential (mv) N/P= Ratio of DNA over Polymer PE-b-PDEAEMA & starting PE retention time (mins) N/P ratio Tan, J.F., Ravi, P.;Too, H.P., Hatton, T.A., Tam, K.C.*, Biomacromolecules (2005), 6,

10 Plasmid DNA interaction with PDEA-b-PE-Biotin PDEA PE Biotin N/P ratio region where polymer unimers coexist with Polymer/DNA complexes Rh (nm) PE-b -PDEAEMA conc. (mg/ml) Delivery of Various Payloads (e.g. drugs, chemicals) using Coated Microgels Journal of Controlled Release (2008) Region 1: ve PDEA decorating on DNA molecules Blue region: loose aggregates comprising of PDEA and DNA Region 2: at high PDEA concentration or large N/P ratio, simplex micelles are produced. In-vitro studies are now underway 10

11 Release Kinetic from Coated Microgels Mechanism Controlling Drug Delivery from Coated Microgels Bare MAA-EA nanogel 3 coated layer nanogel 4 coated layer nanogel PrHy Cross-linked junction PAH PSS 11

12 Fullerene System (Bucky Ball) Drawbacks Solubility Processability Applications Hindered Grafting small groups R R R Well-defined grafting CT Complex N Solutions ph-responsive Fullerene System Polymethacrylic acid-b-c60 PMAA 125 -b-c 60 M n ~10,800 Da M w /M n = 1.18 N N Graft small molecules Graft polymers Charge transfer complexes n N Grafting of Polymers Amphiphilic behaviour CH 2 C n C= H Ravi, P., Dai, S., Tan, C.H., Tam, K.C. Macromolecules (2005), 38, Yu, H., Gan, L. H., Hu, X., Venkatraman, S. S., Tam, K. C., Gan, Y. Y., Macromolecules (2005), 38, Teoh, S.K., Ravi, P., Dai, S., Tam, K.C., Journal of Physical Chemistry B (2005), 109, Ravi, P., Dai, S., Tam, K.C., Journal of Physical Chemistry B (In Press). C( ) 3 12

13 Nano-particles and nano-fractals 1 Nano-particles Nano-fractals Dense Nano-fractals ( nm) f NaCl crystals f NaCl crystals Neutr ralisation Degree 0 Nano-particles ( nm) NaCl crystals on Nano-particles Dense NaCl crystals on Nano-particles 0.0 M NaCl 0.2M NaCl 0.5M NaCl Tan, C.H., Dai, S., Ravi, P., Tam, K.C., Langmuir (2004), 20, Naturally occurring fractal patterns AFM` 13

14 INTERACTIN WITH NN- INIC SURFACTANTS ΔH kj/mol X100 to H2 X100 to PAA a=0 X100 to PAA a=1 X100 to PAA-C60 a=0 X100 to PAA-C60 a=1 C 8 H 17 CH 2 CH 2 n H C TX100 (mm) INTERACTIN WITH NN- INIC SURFACTANTS (b) C 60 -b-paa (a) (b) Rh app (nm) (a) percipitation region (c) (d) CTX100 (mm) (c) (d) C 8 H 17 CH 2 CH 2 n H 14

15 INTERACTIN WITH NN- INIC SURFACTANTS Rh app (nm) (3) C 60 -b-paa C 60 -b-paa-b-c 60 (1) (1) (2) (1) (2) (4) C 8 H 17 CTX100 (mm) CH 2 CH 2 n H RECENT RESEARCH ACTIVITIES in NANTECHNLGY Protein purification MRI Imaging g contrast agents Removal of contaminants Collaborators: Prof. Alan Hatton, MIT Prof. Miranda Yap, BTI (3) (4) ph-responsive microgels Zwiterionic microgels Drug delivery applications Collaborators: Tan CB, Dow Chemicals, S pore Nano-templating Systems Tissue engineering Novel catalysts Collaborators: Prof. Schilen, Lund Univ, Sweden Prof. Yao Jia, Zeijiang Univ, China Drug-polymer interactions Delivery of cancer drugs Development of drug electrodes Collaborators: Prof. Wyn-Jones, Salford, UK 15

16 Self-Assembly Systems for Drug and Gene Delivery Applications Water-soluble Stimuli-responsive Fullerene Systems Dai, S., Ravi, P., Tam, K.C., Soft Matter (2008), 4, 435 Sinaga, A., Hatton, T.A., Tam, K.C., Macromolecules (2007), 40, Tian, Y., Bromberg, L., S.N. Lin, Hatton, T.A., Tam, K.C., J. Controlled Release (2007), 121, 137. Liu, J.H., Sondjaja, R., Tam, K.C., Langmuir (2007), 23, Tan, J.P.K., Tam, K.C., J. Controlled Release (2007), 118, 87. Tan, J.F., Too, H.P., Hatton, T.A., Tam, K.C., Langmuir (2006), 22, Polymer-Surfactant/Drug Interactions Wang C., Ravi, P., Tam, K.C., Langmuir (2007), 23, Wang, C., Wyn-Jones E., Sidhu, J., Tam, K.C., Langmuir (2007), 23, Liao, D.S., Dai, S., Tam, K.C., J. Physical Chemistry B (2007), 111, 371. Tam, K.C., Wyn-Jones, E, Chemical Society Reviews (2006), 35, 693. Wang C., Ravi, P., Tam, K.C., Langmuir (2006), 22, Former Group Members Ravi, P., Dai, S., Wang, C., Tam, K.C., J. Nanoscience & Nanotechnology (2007), 7, Ravi, P., Wang, C., Dai, S., Tam, K.C., Langmuir (2006), 22, Ravi, P., Dai, S., Tam, K.C., J. Physical Chemistry B (2005),109, Ravi, P., Dai, S., Tan, C.H., Tam, K.C, Macromolecules (2005), 38, 933. Responsive and Smart Microgel/Nanogel Systems Tan, B.H., Tam, K.C., Adv. Colloid and Interface Science (2008). Tan, J.P.K., Goh, C.H., Tam, K.C., European J. Pharmaceutical Science, (2007), 32, 340. Tan, B.H., Tam, K.C., Polymer (2007), 48, Tan, B.H., Ravi, P., Tan, L.N., Tam, K.C., J. Colloid & Interfacial Science (2007), 309, Tan, B.H., Ravi, P., Tam, K.C., Macromolecular Rapid Communications (2006), 27,522. Taman Negara July 2004 Phuket March

17 Thank you for your attention I will be happy to answer any questions you may have! Website: animation 17