Dr. Tam's Research Group

This research program focuses on the design of well-defined block copolymers using the atom transfer radical polymerization (ATRP) technique, where polymers of known composition and narrow molecular weight distribution were synthesized. The self-assembly behavior of these systems was elucidated and factors governing their physicochemical properties were quantified as described in our recent publications [1, 4-5, 8-11]. Extending the use of these well-defined block copolymers to the encapsulation and delivery of a cancer drug doxorubicin (DOX) and other model drugs were explored, and the mechanism of binding and release were elucidated. [1-2, 4, 6-7] We identified the important role of electrostatic interaction in enhancing the binding of DOX, and by tuning the pH condition, the balance between the various interactions can be manipulated to control the release kinetics.

Similarly, in gene therapy, the delivery of genetic materials (in the form of genes, gene segments or oligonucleotides) to cell nuclei requires the transfection of DNA to cell and eventually the nucleus. An important scientific issue that has to be addressed is the physics of DNA compaction in the presence of macromolecules. Well-defined poly (ethylene-oxide)-block-poly(2-(diethylamino)ethyl methacrylate) were synthesized by ATRP and the morphological evolution of DNA/polymer complex as a function of the DNA/polymer ratio was elucidated as documented in two recent papers [3, 5]. Such fundamental knowledge is critical for understanding the transfection and delivery to cells, which was recently reported [3]) and further studies are currently in progress.

References:

[1] Tian, Y., Bromberg, L., Lin, S.N., Hatton, T.A., Tam, K.C.*, Journal of Controlled Release (2007), 121 (3), 137-145.

[2] Tan, J.P.K., Tam, K.C.*, Journal of Controlled Release (2007), 118, 87-94.

[3] Tan, J.F., Hatton, T.A., Tam, K.C., Too, H.P.*, Biomacromolecules (2007) 8, 448-454.

[4] Tian, Y., Ravi, P., Bromberg, L., Hatton, T.A., Tam, K.C.*, Langmuir (2007) 23, 2638-2646.

[5] Tan, J.F., Too, H.P., Hatton, T.A.*, Tam, K.C.*, Langmuir (2006), 22, 3744-3750.

[6] Xiong, X.Y., Tam,K.C.*, Gan L.H., Journal of Controlled Release (2005), 108, 263-270.

[7] Xiong, X.Y., Tam, K.C.*, Gan L.H., Journal of Controlled Release (2005), 103, 73-82.

[8] Tan, J.F., Ravi, P.; Too, H.P., Hatton, T.A., Tam, K.C.*, Biomacromolecules (2005), 6, 498-506.

[9] Xiong, X.Y., Tam, K.C.*, Gan L.H., Macromolecules (2004), 37, 3425-3430.

[10] Xiong, X.Y., Tam, K.C.*, Gan L.H., Macromolecules (2003), 36, 9979-9985.

[11] Ravi P., Wang, C., Tam, K.C.*, Gan L.H., Macromolecules (2003), 36, 173-179.

Since the discovery of buckminister fullerene, its potential application is hampered by its strong cohesive nature and insolubility in common organic or aqueous solution. Solubilizing or derivatizing C60 not only obviates the processing problem, but can be an attractive solution to broaden its end-use application. We embarked on a research program to develop water-soluble fullerene systems by preparing well-defined stimuli-responsive fullerene systems. First, stimuli-responsive block copolymers were synthesized via ATRP, and they were then grafted to a single fullerene molecule, yielding an amphiphilic polymer composing of a hydrophobic C60 moiety and a hydrophilic chain segment. These systems self-assembled into various types of nanostructures, depending on the external stimuli and solvent condition, and these morphologies were quantified as reported in several papers [12-15, 17]. We reported for the first time individual fullerene molecules that are solubilized in water, and it offers many potential applications [17]. In the process of preparing samples for transmission electron microscopic analysis, we discovered an unusual phenomenon, where the fullerene polymeric systems in inorganic salt solutions were found to induce the formation of fractals on a nano- to micro dimensions [16]. Work is in progress to elucidate the mechanism of the formation of these fractals.

Based on the new materials developed and a better understanding of these systems, we can now explore their potential applications, such as in the delivery hydrophobic drugs and in cosmetic formulations. As a result of our original contribution, we were invited to contribute a review article [18].

References:

[12] Wang, C., Ravi, P., Dai, S., Tam, K.C.*, Langmuir (2006), 22 (17), 7167-7174.

[13] Ravi, P., Dai, S., Tam, K.C.*, Journal of Physical Chemistry B (2005), 109, 22791-22798.

[14] Teoh, S.K., Ravi, P., Dai, S., Tam, K.C.*, Journal of Physical Chemistry B (2005), 109, 4431-4438.

[15] Ravi, P., Dai, S., Tan, C.H., Tam, K.C.*, Macromolecules (2005), 38, 933-939.

[16] Tan, C.H., Ravi, P., Dai, S., Tam, K.C.*, Langmuir (2004), 20, 9901-9904.

[17] Dai, S., Ravi, P., Tan, C. H., Tam, K.C.*, Langmuir (2004), 20, 8569-8575.

[18] Ravi, P., Dai, S., Wang, C., Tam, K.C.*, Journal of Nanoscience and Nanotechnology (2007), 7 (4-5), 1176-1196.

In a series of papers [19-26] on binding interactions between surfactant and water-soluble polymers, our group has advanced new understanding on the binding mechanism between anionic and cationic surfactants and various types of water-soluble polymers. In most pharmaceutical and home care product formulations, co-solvents and surfactants are commonly utilized to achieve the desired performance. Thus, the interactions between surfactants and polymers in such formulation are critical to the development of a successful product. The emphasis of our research is to elucidate the interactions between associative polymers and various kinds of surfactants commonly found in water-borne coating systems. We utilized a combination of various experimental techniques, such as isothermal titration calorimetry, light scattering, and surfactant selective electrodes to elucidate the interaction mechanisms between different types of polymers and surfactant systems.

By carefully combining the correct experimental techniques, we developed further insights on the interaction between SDS and poly(ethylene-oxide). We identified the critical segment length with molar mass of 400 Da, beyond which the rehydration of PEO chains from water produces SDS-PEO complex comprising of PEO chains wrapping around the SDS micelles [21]. We extended this finding to elucidate the binding mechanism between SDS and hydrophobically modified PEO (HEUR) and observed for the first time the formation of large aggregates connecting several rosette micelles, which are stabilized by SDS molecules [22, 24]. Our latest finding using electromotive force technique confirmed the un-cooperative binding of SDS monomers and hydrophobic domains of HEUR, and a physical mechanism describing the interaction between SDS and HEUR polymers containing different hydrophobic moieties was proposed [24]. We observed for the first time two different binding mechanisms between SDS and poly(propylene-oxide) (PPO) above and below the cloud point, and this new fundamental understanding has recently been published [25].

A natural extension of the work on SDS/PEO system is to examine the binding interaction between cationic surfactant and anionic polyelectrolyte systems. The binding interactions between various types of cationic surfactants and anionic polyacrylic acids or hydrophobically modified polyelectrolyte systems at different ionization degrees were examined. We reported additional insights on the binding interactions as a function of ionization and surfactant concentrations [23, 26].

Currently, we are extending the techniques and knowledge gained to elucidate the binding of drug and biological molecules with block copolymers and dendrimers, and some interesting results have recently been published [19, 20].

References:

[19] Wang, C., Wyn-Jones E., Sidhu, J., Tam, K.C.*, Langmuir (2007), 23, 1635-1639.

[20] Wang C., Ravi, P., Tam, K.C.*, Langmuir (2006), 22, 2927-2930.

[21] Dai, S., Tam, K.C.*, J. Phys. Chem. B (2006), 110, 20794-20800.

[22] Dai, S., Tam, K.C.*, Langmuir (2005), 21, 7136-7142.

[23] Wang, C., Tam, K.C.*, Journal Physical Chemistry B, (2004), 108, 8976-8982.

[24] Dai, S., Tam, K.C.*, Wyn-Jones, E., Jenkins, R.D., J. Phys. Chem. B (2004), 108, 4979-4988.

[25] Dai, S., Tam, K.C.*, Langmuir (2004), 20, 2177-2183.

[26] Wang, C., Tam, K.C.*, Langmuir (2002) 18, 6484-6490

This research program was started in 1993 through an industrial collaboration with Union Carbide (now Dow Chemicals), which then received additional funding from the Ontario-Singapore Grant Scheme for collaboration with Professor Mitch Winnik at the University of Toronto. We designed a series of model associative polymers, where the synthesis of the polymers were carried out at Dow research laboratories in USA and Singapore. The extensive published works on hydrophobically modified alkali-soluble emulsion systems (HASE) reported since 1997 are largely attributed to our research group.

The objectives of the project are to elucidate the dissolution and association behavior of the HASE polymers. Using a combination of several physical experimental techniques, we were able to provide fundamental knowledge on the following:

(i) The dissolution mechanism during the neutralization process, where we reported for the first time the formation of polymer chain clusters consisting of 5 to 7 polymer chains after the latex dispersions were completely solubilized in an alkali medium [27-28].

(ii) The roles of chemical architecture, e.g. ethylene-oxide spacer chain, size of hydrophobes on the microstructure, and bulk rheological properties were determined. We observed a multi-nodal hydrophobic domain, where the strength of these hydrophobic domains was correlated to the bulk rheological properties [29].

(iii) We were able to elucidate the state of the polymer network under varying deformations using the superposition of oscillation on steady shear flows and to correlate and model the destruction of the network by applied forces and cyclodextrins [30].

We recently extended this research by preparing cross-linked nanogel systems based on the prior knowledge developed, and the potential of using these materials as colloidal scaffold and drug delivery vehicles is currently being explored [31-32].

References:

[27] Wang, C., Tam, K.C.*, Jenkins, R.D., Journal of Physical Chemistry B, (2002), 106, 1195-1204.

[28] Dai, S., Tam, K.C.*, Jenkins, R.D., Macromolecular Chemistry Physics (2002) 203, 2312-2321.

[29] Dai, S., Tam, K.C.*, Jenkins, R.D., Macromolecules (2001), 34 (14), 4673-4675.

[30] Liao, D.S., Dai, S., Tam, K.C.*, Macromolecules (2007), 40, 2936-2945.

[31] Tan, B.H., Ravi, P., Tan, L.N., Tam, K.C.*, Journal of Colloid & Interfacial Science (2007), 309 (2), 453-463.

[32] Tan, B.H., Tam, K.C.*, Lam Y.C., Tan C.B., Advances in Colloid and Interface Science, (2005), 113, 111-120.