title: PEGylated lipid nanocapsules with improved drug encapsulation and controlled release properties.
abstract: Drugs with poor lipid and water solubility are some of the most challenging to formulate in nanocarriers, typically resulting in low encapsulation efficiencies and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are known for their amenability to diverse modifications that allow the formation of domains with different physicochemical properties, an interesting feature to address a drug encapsulation problem. We explored this problem by encapsulating in PEG-NC the promising anticancer drug candidate F10320GD1, used herein as a model for compounds with such characteristics. The nanocarriers were prepared from Miglyol(®), lecithin and PEG-sterate through a solvent displacement technique. The resulting system was a homogeneous suspension of particles with size around 200 nm. F10320GD1 encapsulation was found to be very poor (<15%) if PEG-NC were prepared using water as continuous phase; but we were able to improve this value to 85% by fixing the pH of the continuous phase to 9. Interestingly, this modification also improved the controlled release properties and the chemical stability of the formulation during storage. These differences in pharmaceutical properties together with physicochemical data suggest that the pH of the continuous phase used for PEG-NC preparation can modify drug allocation, from the external shell towards the inner lipid core of the nanocapsules. Finally, we tested the bioactivity of the drug-loaded PEG-NC in several tumor cell lines, and also in endothelial cells. The results indicated that drug encapsulation led to an improvement on drug cytotoxicity in tumor cells, but not in non-tumor endothelial cells. Altogether, the data confirms that PEG-NC show adequate delivery properties for F10320GD1, and underlines its possible utility as an anticancer therapy.
authors.forename: Pablo
authors.initials: P
authors.lastname: Hervella
authors.forename: Maria
authors.initials: M
authors.lastname: Alonso-Sande
authors.forename: Francisco
authors.initials: F
authors.lastname: Ledo
authors.forename: Maria L
authors.initials: ML
authors.lastname: Lucero
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Alonso
authors.affiliation: Ed. CIMUS T6D1, Av. Barcelona s/n, Campus Vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. marcos.garcia@usc.es.
authors.forename: Marcos
authors.initials: M
authors.lastname: Garcia-Fuentes
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D053769:Nanocapsules / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D053769:Nanocapsules; D011092:Polyethylene Glycols