Grinstaff Group - BME/Chemistry - Boston University

Polyglycerol Carbonates

Overview

Glycerol based polymers are of widespread interest for industrial, cosmetic, and pharmaceutical applications. Various polymer architectures from linear to dendritic are reported for pure polyglycerol ethers and carbonates as well as coploymers with hydroxy-acids, for example, to give poly ether-esters or poly carbonate-esters. Within the biomedical arena, these polymers possess the following advantages: 1) a free hydroxyl for functionalization with chemotherapeutic agents, antibacterial compounds, anti-inflammatory agents, fluorescent tags, or material property modifiers; 2) a defined biodegradation route to afford non-toxic and non-acidic byproducts - e.g., glycerol and carbon dioxide; 3) physical properties ranging from semi-crystalline or amorphous materials based on the polymer or co-polymer composition; and 4) amenability to manufacturing methods such as casting or electrospinning. In many ways, these polymers provide users the capabilities of well-known polymers like PLA (polylactic acid) or PLGA (poly(lactic-co-glycolic acid)) with the additional benefits of an easily modifiable structure and non-acidic products upon biodegradation. These advantages have been put to use, and poly(1,3-glycerol carbonate) based biomaterials are being investigated as drug-loaded buttressing films for the prevention of tumor recurrence after surgical resection, nanoparticles for drug delivery, and coatings for prevention of seroma. However, linear poly(1,2-glycerol carbonate)s are far less explored and yet, one would hypothesize that these materials would degrade more readily than the 1,3-glycerol analogs fulfilling an unmet need for readily degradable biocompatible polycarbonates.

Synthesis & Characterization

Poly(1,2-glycerol carbonate)s are synthesized via a facile and efficient method by coupling a readily available starting material benzyl glycidyl ether with carbon dioxide using [SalcyCoIIIX] complexes. The hydrolytic kinetic resolution of benzyl glycidyl ether using Jacobsen’s catalyst and subsequent polymerization to afford the chiral polymer with isotactic backbone, the deprotection of the benzyl to afford poly(1,2-glycerol carbonate)s. Poly(1,2-glycerol carbonate)s degrade significantly faster than poly(1,3-glycerol carbonate) with t1/2 of ~2-3 days. No degradation occurred over the 4 day period of the poly(1,3-glycerol carbonate). We attribute this increase in degradation to the lower activation energy required for intramolecular attack of the pendant primary hydroxyl, compared to the secondary hydroxyl group in poly(1,3-glycerol carbonate), to the carbonate linkage with formation of the thermodynamically stable 5-membered cyclic glycerol carbonate.Next, the terpolymerization of benzyl glycidyl ether, propylene oxide and CO2 using both a binary [rac-SalcyCoIIIDNP]/PPNDNP system and a bifunctional [rac-SalcyCoIIIDNP] bearing a quaternary ammonium salt is studied. Rheological studies on cast molds of the polymers showed both poly(benzyl 1,2-glycerol carbonate) (PBGC), poly(benzyl 1,2-glycerol-co-propylene carbonate) (PBGC-co-PC)) and the deprotected poly(1,2-glycerol-co-propylene carbonate) (PGC-co-PC)) exhibited tough mechanical properties. As shown in Figure 6, in the 1 Hz to 3 Hz region the storage modulus (G’) and loss modulus (G’’) of the PBGC with a molecular weight of 30.3 kg/mol ranged from 2.0×105 to 3.4×105 Pa and 2.0×105 to 3.8×105 Pa, respectively. Incorporation of 40% of propylene carbonate unit in the polymer chain (Mn = 32.3 kg/mol) resulted in a ~7 times increase in both G’ and G’’. Compared to the protected version, the debenzylated copolymer PGC-co-PC (60% GC, Mn = 17.3 kg/mol) showed a lowered G’ and G’’, and the values ranged from 4.37×105 to 9.51×105 Pa and 5.21×105 to 1.14×106 Pa, respectively. However, these values were still 2 to 3 times greater than those measured for pure PBGC.

Selected Publications

Boston University College of Engineering Department of Biomedical Engineering Boston University Department of Chemistry Boston University