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    Thermo-responsive lipophilic NIPAM-based block copolymers as stabilizers for lipid-based cubic nanoparticles

    Year: 2022

    Journal: Colloid Surf. B-Biointerfaces, Volume 220, DEC

    Authors: Balestri, Arianna; Lonetti, Barbara; Harrisson, Simon; Farias-Mancilla, Barbara; Zhang, Junliang; Amenitsch, Heinz; Schubert, Ulrich S.; Guerrero-Sanchez, Carlos; Montis, Costanza; Berti, Debora

    Organizations: MIUR-Italy (Progetto Dipartimenti di Eccellenza 2018-2022, allocated to Department of Chemistry Ugo Schiff); Agence Nationale de la Recherche (ANR, France) [ANR-15-CE08-0039]; Deutsche Forschungsgemeinschaft (DFG, Germany) [316213987]

    Keywords: Cubosomes; Amphiphilic block copolymer; Stabilizer; Model membrane; Drug delivery

    The design of drug delivery systems (DDS) for the encapsulation of therapeutic agents and the controlled release to the target site of the disease is one of the main goals of nanomedicine. Although already explored in an extensive number of studies over the years, lipid assemblies, and particularly liposomes, are still considered the most promising and interesting candidates as DDS due to their biocompatibility and structural similarity with plasma membranes. Lately, this research area has been extended to include more complex lipid assemblies, such as cubosomes. Cubosomes are an emerging structural platform for the delivery of molecules with pharmaceutical interest, such as drugs, bioactives and contrast agents. Here we report on the application of a thermo-responsive copolymer poly(N,N-dimethylacrylamide)-block-poly(N-isopropylacrylamide) (PDMA-b-PNIPAM), as a thermoresponsive stabilizer of lipid-based nanoparticles for drug-delivery. First, we assessed the affinity of PDMA-bPNIPAM towards supported and free-standing bilayers; then, we explored the colloidal and thermoresponsive properties of cubic self-assembled DDS composed of glycerol-monooleate (GMO), where PDMA-b-PNIPAM replaces the conventional stabilizer Pluronic F127 (PEOx-PPOy-PEOx), normally used for cubosomes. We prepared dispersions of cubic lipid nanoparticles with two PDMA-b-PNIPAM block copolymers of different molar mass. The colloidal properties were then assessed and compared to those exhibited by standard lipid cubic dispersions stabilized by Pluronic F-127, combining a series of experimental techniques (Quartz Crystal Microbalance with Dissipation monitoring, Dynamic Light Scattering, Small-Angle X-rays Scattering, Cryo-Transmission Electron Microscopy). Interestingly, PDMA-b-PNIPAM stabilized cubosomes display additional benefits with respect to those stabilized by Pluronic, thanks to the combination of a sponge effect for the controlled release of encapsulated molecules and an increased affinity towards lipid bilayer membranes, which is a promising feature to maximize fusion with the target-cellular site.
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