Olivier Halleux

Amphiphilic copolymers of epsilon-caprolactone and gamma-substituted epsilon-caprolactone. Synthesis and functionalization of poly(D,L-lactide) nanoparticles

Fully biodegradable and surface-functionalized poly(D,L-lactide) (PLA) nanoparticles have been prepared by a co-precipitation technique. Novel amphiphilic random copolyesters P(CL-co-γ XCL) were synthesized by controlled copolymerization of ε-caprolactone and ε-caprolactone substituted in the γ-position by a hydrophilic X group, where X is either a cationic pyridinium (γ PyCL) or a non-ionic hydroxyl (γ OHCL). Nanoparticles were prepared by co-precipitation of PLA with the P(CL-co-γ XCL) copolyester from a DMSO solution. Small amounts of cationic P(CL-co-γ PyCL) copolymers are needed to quantitatively form stable nanoparticles (ca. 10 mg/100 mg PLA), although larger amounts of non-ionic P(CL-co-γ OHCL) copolymers are needed (⩾12.5 mg/100 mg PLA). Copolymers with a low degree of polymerization (ca. 40) are more efficient stabilizers, probably because of faster migration towards the nanoparticle–water interface. The nanoparticle diameter decreases with the polymer concentration in DMSO, e.g. from ca. 160 nm (16 mg/ml) to ca. 100 nm (2 mg/ml) for PLA/P(CL-co-γ PyCL) nanoparticles. Migration of the P(CL-co-γ XCL) copolyesters to the nanoparticle surface was confirmed by measurement of the zeta potential, i.e. ca. +65 mV for P(CL-co-γ PyCL) and –7 mV for P(CL-co-γ OHCL). The polyamphiphilic copolyesters stabilize PLA nanoparticles by electrostatic or steric repulsions, depending on whether they are charged or not. They also impart functionality and reactivity to the surface, which opens up new opportunities for labelling and targeting purposes.

Novel functionalization routes of poly(ε-caprolactone)

The aluminum alkoxide mediated ring opening polymerization of functional lactones, such as γ-ethylene ketal-ϵ-caprolactone (TOSUO), γ-(triethylsilyloxy)-ϵ-caprolactone (SCL) and γ-bromo-ϵ-caprolactone (γBrCL), is a versatile route to polyesters containing ketal, ketone, alcohol and bromide groups. As result of living polyaddition mechanism, random and block copolymerization of ϵCL and γBrCL has been successfully carried out. The reactivity ratios are quite similar (1.08 for ϵ-CL, and 1.12 for γBrCL). These random copolymers are semicrystalline when they contain less than 30 mol% of γBrCL, otherwise they are amorphous. No transesterification reaction occurs during the sequential polymerization of ϵ-CL and γBrCL leading to block copolymers. Reaction of poly(ϵCL-co-γBrCL) with pyridine provides quantitatively a polycationic polyester. Furthermore, the reaction of this random copolymer with 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) is a route to unsaturated polyesters, whose the non conjugated double bonds can be quantitatively converted into epoxides by reaction with m-chloroperbenzoic acid (mCPBA). No chain degradation is detected during these derivatization reactions of poly(ϵCL-co-γBrCL).