Freeze-Drying and Lyopreservation of Diblock and Triblock Poly(Lactic Acid)–Poly(Ethylene Oxide) (PLA–PEO) Copolymer Nanoparticles

Abstract
In this study, the formulation and process parameters that determine successful production and long-term stability of freeze-dried poly(lactic acid) (PLA) nanoparticles with “hairy-like” poly(ethylene oxide) (PEO) surfaces were investigated. Nanoparticles with grafted (covalently bound) PEO coatings were produced by the salting-out method from blends of PLA and PLA–PEO diblock or triblock copolymers. PLA nanoparticles with physically adsorbed PEO were also produced. The redispersibility of the nanoparticles after freeze-drying under various conditions was assessed. The surface of the nanoparticles was characterized and classified in terms of “brush” and “loop” conformations. Upon freeze-drying, it appeared that the presence of PEO at the nanoparticle surface could severely impair the redispersibility of the particles, especially in the PEO-grafted systems. This effect was shown to be related to the amount and molecular weight of PEO in the various formulations. In most cases, particle aggregation was prev...

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