title: EXPLOITING THE VERSATILITY OF CHOLESTEROL IN NANOPARTICLES FORMULATION.
abstract: The biocompatibility of polymers, lipids and surfactants used to formulate is crucial for the safe and sustainable development of nanocarriers (nanoparticles, liposomes, micelles, and other nanocarriers). In this study, Cholesterol (Chol), a typical biocompatible component of liposomal systems, was formulated in Chol-based solid nanoparticles (NPs) stabilized by the action of surfactant and without the help of any other formulative component. Parameters as type (Solutol HS 15, cholic acid sodium salt, poly vinyl alcohol and Pluronic-F68), concentration (0.2; 0.5 and 1% w/v) of surfactant and working temperature (r.t. and 45°C) were optimized and all samples characterized in terms of size, zeta potential, composition, thermal behavior and structure. Results demonstrated that only Pluronic-F68 (0.5% w/v) favors the organization of Chol chains in structured NPs with mean diameter less than 400nm. Moreover, we demonstrated the pivotal role of working temperature on surfactant aggregation state/architecture/stability of Chol-based nanoparticles. At room temperature, Pluronic-F68 exists in solution as individual coils. In this condition, nanoprecipitation of Chol formed the less stable NPs with a 14±3% (w/w) of Pluronic-F68 prevalently on surface (NP-Chol/0.5). On the contrary, working near the critical micelle temperature (CMT) of surfactant (45°C), Chol precipitates with Pluronic-F68 (9±5% w/w) in a compact stable matricial structure (NP-Chol/0.5-45). In vitro studies highlight the low toxicity and the affinity of NP-Chol/0.5-45 for neuronal cells suggesting their potential applicability in pathologies with a demonstrated alteration of neuronal plasticity and synaptic communication (i.e. Huntington's disease).
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Belletti
authors.affiliation: WG Molecular Analysis of Synaptopathies, Neurology Dept., Neurocenter of Ulm University, Ulm, Germany; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Grabrucker
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pederzoli
authors.affiliation: WG Molecular Analysis of Synaptopathies, Neurology Dept., Neurocenter of Ulm University, Ulm, Germany; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Menrath
authors.affiliation: Center for Nanotechnology, Innovation@NEST, Istituto Italiano di Tecnologia, Pisa, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Cappello
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Vandelli
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Forni
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tosi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Ruozi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D004339:Drug Compounding; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
chemical_list: D002784:Cholesterol
keywords: Cholesterol; Pluronic-F68; formulation conditions; nanoparticles; neuronal cells