Nanoscopic core-shell drug carriers made of amphiphilic triblock and star-diblock copolymers

The aim of this work was to design injectable nanocarriers for drug delivery based on PCL–PEO amphiphilic block copolymers with linear ABA triblock and 4-armed (BA)4 star-diblock architectures (A = PEO, B = PCL). The copolymers were obtained by coupling of a monofunctional –COOH end-capped PEO (Mn = 2.0 kDa) with linear or 4-armed star-shaped PCL macromers bearing –OH terminal groups and were characterized by 1H NMR spectroscopy and size exclusion chromatography. DSC and X-ray diffraction experiments showed that separate crystalline phases of PCL and PEO are present in bulk copolymers. Nanoparticles were produced by nanoprecipitation (NP) and by a new melting-sonication procedure (MS) without the use of toxic solvents, and characterized for size, polydispersity, zeta potential and core-shell structure. Nanoparticles were loaded with all-trans-retinoic acid (atRA) as a model drug and their release features assessed. Results demonstrate that both techniques allow the formation of PEO-coated nanoparticles with a hydrodynamic diameter that is larger for nanoparticles prepared by MS. atRA is released from nanoparticles at controlled rates depending on size, loading and, more important, preparation technique, being release rate faster for MS nanoparticles. Some biorelevant properties of the carrier such as complement activation were finally explored to predict their circulation time after intravenous injection. It is demonstrated that nanoparticles prepared by MS do not activate complement and are of great interest for future in vivo applications.