title: Balancing the effect of corona on therapeutic efficacy and macrophage uptake of lipid nanocapsules.
abstract: Several studies have shown the potential of biocompatible lipid nanocapsules as hydrophobic drug delivery systems. Understanding the factors that determine the interactions of these oil-in-water nanoemulsions with cells is a necessary step to guide the design of the most effective formulations. The aim of this study was to probe the ability of two surfactants with a markedly different nature, a non-ionic poloxamer, and a charged phospholipid, to prepare formulations with shells of different composition and different surface properties. Thus we determined their effects on the interaction with biological environments. In particular, we investigated how the shell formulation affected the adsorption of biomolecules from the surrounding biological fluids on the nanocapsule surface (corona formation). A complete physicochemical characterization including an isothermal titration calorimetry (ITC) study revealed that the use of poloxamer led to nanocapsules with a marked reduction in the number of protein-binding sites. Surface hydrophilicity and changes in corona formation strongly correlated to changes in uptake by cancer cells and by macrophages. Our results indicate that the nature and concentration of surfactants in the nanocapsules can be easily manipulated to effectively modulate their surface architecture with the aim of controlling the environmental interactions, thus optimizing functionality for in vivo applications. In particular, addition of surfactants that reduce protein binding can modulate nanoparticle clearance by the immune system, but also screens the desired interactions with cells, leading to lower uptake, thus lower therapeutic efficacy. The two effects need to be balanced in order to obtain successful formulations.
authors.affiliation: Biocolloid and Fluid Physics Group, Department of Applied Physics, University of Granada, 18071 Granada, Spain; European Center for Nanomedicine (CEN), Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, 20131, Italy. Electronic address: paola.sanchez@polimi.it.
authors.forename: P
authors.initials: P
authors.lastname: Sánchez-Moreno
authors.affiliation: Department of Physical Chemistry, University of Granada, 18071 Granada, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Buzón
authors.affiliation: Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18100, Spain; Department of Human Anatomy and Embriology, Biosanitary Institute of Granada (ibs. GRANADA), University Hospitals of Granada-University of Granada, 18012 Granada, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Boulaiz
authors.affiliation: Biocolloid and Fluid Physics Group, Department of Applied Physics, University of Granada, 18071 Granada, Spain; Department of Applied Physics II, University of Málaga, 29071 Málaga, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Peula-García
authors.affiliation: Biocolloid and Fluid Physics Group, Department of Applied Physics, University of Granada, 18071 Granada, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Ortega-Vinuesa
authors.affiliation: Department of Physical Chemistry, University of Granada, 18071 Granada, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Luque
authors.affiliation: Faculty of Mathematics and Natural Sciences, Pharmacokinetics, Toxicology and Targeting - Groningen Research Institute of Pharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Salvati
authors.affiliation: Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18100, Spain; Department of Human Anatomy and Embriology, Biosanitary Institute of Granada (ibs. GRANADA), University Hospitals of Granada-University of Granada, 18012 Granada, Spain. Electronic address: jmarchal@ugr.es.
authors.forename: J A
authors.initials: JA
authors.lastname: Marchal
mesh_terms: D065966:Absorption, Physicochemical; D000327:Adsorption; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004058:Diffusion; D000077143:Docetaxel; D006801:Humans; D008264:Macrophages / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D010743:Phospholipids / Q000737:chemistry*; D000066970:Protein Corona / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D053769:Nanocapsules; D010743:Phospholipids; D000066970:Protein Corona; D013501:Surface-Active Agents; D043823:Taxoids; D000077143:Docetaxel
keywords: Cancer; Docetaxel; ITC; Lipid nanocapsules; Poloxamer; Protein corona