59th Annual Report on Research 2014

This project involves the the creation of dynamic polymers and polymer networks for forming new polymeric hydrogels. Networks are formed based on non-covalently crosslinking hydrophobic and hydrophilic polymer chains. The basic linking units are derived from sequence-specific molecular duplexes that are equipped with both multiple hydrogen-bonding and disulfide bond-forming ability. These duplexes, derived from H-bonded duplexes we developed, are capable of mediating highly specific association and covalent crosslinking in both nonpolar and polar (including aqueous) media. Our proposed objectives are (1) to modify commercially available, biocompatible polymer chains including poly(lactic acids) (PLA) and poly(ethylene glycol)(PEG) chains with our linking units, (2) form libraries of amphiphilic dynamic covalent diblock, triblock and multi-block copolymers with various, readily adjustable PLA/PEG ratios mediated by the introduced duplex units, and (3) to correlate the effect of PLA/PEG (thus the hydrophobic/hydrophilic) ratios on gelating ability of the resultant amphiphilic block copolymers.

Over the past four years (the 4th year involved a no-cost extension), we elucidated the conditions for coupling PLA and PEG chains of various lengths. PLA and PEG chains with molecular weights ranging from 1,000 to 5,000 end-modified with our duplex-forming units are successfully and efficiently coupled, leading to the formation of diblock and triblock copolymers. The resultant block copolymers have been characterized with ¹H NMR and GPC, results from which have demonstrated the expected high efficiency of our method. Figure 1a show the GPC traces of PEG₅₀₀₀-PLA₅₀₀₀, one of the diblock copolymers prepared.

Figure 1. (a) GPC traces of PEG₅₀₀₀-PLA₅₀₀₀ (red, retention time = 5.23 min), PEG₅₀₀₀ (blue, retention time = 5.57 min), and PLA₅₀₀₀ (black, retention time = 5.76 min) eluted with THF (1 mL/min) at 35 ^oC. (b) TEM image of PEG5000-PLA5000 micelles.

The obtained diblock copolymers were examined for their micellation in aqueous media. Dynamic light scattering (DLS) showed that the micelles all have unimodal size distribution, with average diameters ranging from 34 nm to over 100 nm. Transmission electron microscopy (TEM) demonstrated that the micelles are all spherical (Figure 1b). The polymeric micelles were stable for weeks in water. Upon adding a free thiol (DTT), the polymeric micelles disintegrate quickly due to the cleavage of disulfide linkages that connect that PEG and PLA blocks.

We have also made major progress in ligating different ratios of PEG and PLA chains into linear amphiphilic multiblock copolymers, which offers a general strategy for adjusting the overall hydrophilicity and hydrophobicity of the corresponding multi-block copolymers. The gelating ability of some of these multi-block copolymers have being assessed, which revealed very promising properties including tunable thermo-reversibility. On another front, by introducing branched crosslinkers, we tested the construction of covalently cross-linked networks of hydrophilic polymer chains. Polymeric networks with different crosslinking densities and thus different mechanical strength, were obtained. The latest results have been reported in three recent publications.