1924
Biomacromolecules 2008, 9, 1924–1933
Biodegradable Polycarbonate-b-polypeptide and Polyester-b-polypeptide Block Copolymers: Synthesis and Nanoparticle Formation Towards Biomaterials Maude Le Hellaye, Nicolas Fortin, Julien Guilloteau, Alain Soum, Sebastien Lecommandoux,* and Sophie M. Guillaume* Laboratoire de Chimie des Polyme`res Organiques, LCPO, Universite´ Bordeaux 1-CNRSsENSCPB, 16 Avenue Pey-Berland, 33607 Pessac Cedex, France Received February 18, 2008; Revised Manuscript Received April 16, 2008
The amino poly(trimethylene carbonate)-NHt-Boc (PTMC-NHt-Boc) and poly(ε-caprolactone)-NHt-Boc (PCLNHt-Boc) were synthesized by ring-opening polymerization (ROP) of TMC or CL and subsequently deprotected into the corresponding PTMC-NH2 and PCL-NH2. These functional homopolymers were used as macroinitiators for the ROP of γ-benzyl-L-glutamate N-carboxyanhydride (BLG), consequently, giving the respective diblock copolymers PTMC-b-PBLG and PCL-b-PBLG in almost quantitative yields. The (co)polymers have been characterized by NMR and SEC analyses. DSC and IR studies confirmed the block structure of the copolymers and highlighted a phase separation between the rigid peptide (R-helix conformation) and the more flexible polyester segments. The self-assembly and the degradation behaviors of the copolymers depended on the nature of the polyester block and on the copolymer composition. Nanoparticles obtained from PBLG block copolymers were twice smaller (RH < 100 nm) than those formed from PTMC and PCL homopolymers. Finally, their enzymatic degradation revealed that PTMC nanoparticles degraded faster than those made of PCL.
Introduction Due to their unique properties, degradable polymers have long been considered as environmentally friendly polymers and the spectacular advances achieved over the past three decades in the synthesis, manufacture, and processing of these materials have given rise to a broad range of practical applications ranging from packaging to more sophisticated biomedical devices.1–5 Among the great variety of degradable polymers, linear aliphatic polyesters are particularly attractive and mostly used in both biomedical and pharmaceutical applications because of their low toxicity, their hydrolytic and enzymatic degradability, and their versatility regarding physical, chemical, and biological properties.6 Because R-amino acids are naturally occurring compounds in living systems and in molecules presenting a biological activity, the synthesis of biodegradable, biocompatible, and a fortiori nontoxic poly(R-amino acid)s has attracted growing interest. Poly(R-amino acid)s are especially used as natural protein models for the study of different biological processes but, more recently, they have found applications in the area of “polymer therapeutics”, especially as biomedical devices and nanoparticules.7–9 Depending on the amino acid side-chain substituents, polypeptides can hierarchically assemble into stable ordered conformations (helices, sheets or turns secondary structures, tertiary and quaternary assemblies).10 The synthesis of polypeptides that can self-assemble into non-natural structures is, thus, an attractive challenge for polymer chemists. * To whom correspondence should be addressed. Present address: Laboratoire Catalyse et Organome´talliques, CNRS-Universite´ de Rennes 1, Sciences Chimiques de Rennes (UMR 6226), Campus de Beaulieu, 35042 Rennes Cedex, France. Phone: (+33)2 2323 5880. Fax: (+33)2 2323 6939. E-mail:
[email protected] (S.M.G.); Phone: (+33)5 4000 2241. Fax: (+33)5 4000 8487. E-mail:
[email protected] (S.L.).
One reason for the growing interest in these degradable polyesters is that their physical and chemical properties can be varied over a wide range by, for example, copolymerization and advanced macromolecular engineering.11 Associating polypeptides to polyesters in copolymer architectures upon monitoring and controlling the nature and the composition of each block would provide functionalized side chains (through R-amino acid residues), would allow tuning the amphiphilic character and degradation patterns of the polymers as well as would favor interactions with other peptides or proteins, thereby giving access to versatile original materials.12–16 Herein, we report on the synthesis, characterization, and selfassembly properties of poly(trimethylene carbonate)-b-poly(γbenzyl L-glutamate) (PTMC-b-PBLG) and poly(ε-caprolactone)b-poly(γ-benzyl L-glutamate) (PCL-b-PBLG). They have been synthesized by sequential ring-opening polymerization (ROP) of TMC or CL and BLG. These block copolymers, which include the first example of poly(trimethylene carbonate)-bpolypeptide diblock copolymers, have been characterized and subsequently used to prepare biodegradable nanoparticles.
Experimental Section Materials. All manipulations were performed under inert atmosphere (argon, nitrogen;
