(532g) Biomaterials Based on Polyethylene Glycol-Dihydroxyacetone Block Copolymers

Polymeric biomaterials have played an integral role in the fields of tissue engineering, biomedical devices, and targeted drug delivery. Block copolymers, consisting of hydrophilic and hydrophobic segments, are especially important because of the ability to control their physical and chemical properties by adjusting the ratio, size, and type of constituting blocks. Polyethylene glycol (PEG)-based block copolymers have received much attention in this field because of PEG's favorable biological and chemical properties. The amphiphilic nature of these diblock copolymers allows them to form micelles in aqueous solution environments for potential use in a wide range of applications, including drug delivery.

There is an ongoing effort to synthesize polymeric biomaterials with non-toxic degradation products. One approach is to synthesize these materials using building blocks that exist naturally in the human body. Our current focus is on the synthesis of new biomaterials based on dihydroxyacetone (DHA, I). DHA is a metabolic intermediate of glucose, and is FDA-approved as the active ingredient in sunless tanning lotions. A synthetic route was devised to lock DHA in its monomeric form via acetalization of the C2 carbonyl functionality (III). Ring closure allowed the formation of cyclic 2,2-dimethoxypropylene carbonate (IV). The PEG-DHA (MPEG-pDHA, VI) based diblock copolymer was obtained by the ring opening polymerization of IV in the presence of monomethoxy-PEG (MPEG, V; Mn = 5000) and stannous octoate. The length of the pDHA block could be controlled by adjusting the reactant feed ratios and initiator injection conditions (Mn = 3000, 5000, and 10000). The MPEG-pDHA was subsequently deprotected to form MPEG-dpDHA (VII) (Scheme 1). The intermediates and final products were characterized by 1H NMR, GPC, DOSY, DSC, and TGA analysis. This polymer incorporates some of the physical, chemical, and biological properties of both its constituting blocks. The dpDHA hompolymer is insoluble in water and most common organic solvents, but is hydrophilic based on contact angle measurements. This, coupled with PEG's solubility characteristics, allows the block copolymer to form micelles in hydrophilic solvents even though both constituting blocks are hydrophilic in nature. Dynamic light scattering and TEM results indicated the formation of micelles with an average diameter of 45 nm in water and 70 nm in ethanol (Figure 1), giving it potential for use in systemic drug delivery applications.