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

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Abstract
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.