title: Nucleolipid nanovectors as molecular carriers for potential applications in drug delivery.
abstract: Novel thymidine- or uridine-based nucleolipids, containing one hydrophilic oligo(ethylene glycol) chain and one or two oleic acid residues (called ToThy, HoThy and DoHu), have been synthesized with the aim to develop bio-compatible nanocarriers for drug delivery and/or produce pro-drugs. Microstructural characterization of their aggregates has been determined in pure water and in pseudo-physiological conditions through DLS and SANS experiments. In all cases stable vesicles, with mean hydrodynamic radii ranging between 120 nm and 250 nm have been revealed. Biological validation of the nucleolipidic nanocarriers was ensured by evaluation of their toxicological profiles, performed by administration of the nanoaggregates to a panel of different cell lines. ToThy exhibited a weak cytotoxicity and, at high concentration, some ability to interfere with cell viability and/or proliferation. In contrast, DoHu and HoThy exhibited no toxicological relevance, behaving similarly to POPC-based liposomes, widely used for systemic drug delivery. Taken together, these results show nucleolipid-based nanocarriers as finely tunable, multi-functional self-assembling materials of interest for the in vivo transport of biomolecules or drugs.
authors: Dipartimento di Chimica Organica e Biochimica, Università degli Studi di Napoli Federico II, Complesso Universitario di Monte S. Angelo, via Cinthia, 80126 Naples, Italy.
authors: Luca
authors: L
authors: Simeone
authors: Gaetano
authors: G
authors: Mangiapia
authors: Carlo
authors: C
authors: Irace
authors: Antonio
authors: A
authors: Di Pascale
authors: Alfredo
authors: A
authors: Colonna
authors: Ornella
authors: O
authors: Ortona
authors: Lorenzo
authors: L
authors: De Napoli
authors: Daniela
authors: D
authors: Montesarchio
authors: Luigi
authors: L
authors: Paduano
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D009829:Oleic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity
chemical_list: C572326:3-(4-pyridylmethyl)-2',3'-di-O-oleyl-5'-O-(benzyloxy)hexaethylene glycol-acetyl-uridine; C572325:3-(4-pyridylmethyl)-3'-O-oleyl-5'-O-(benzyloxy)hexaethylene glycol-acetyl-thymidine; C572324:3-(4-pyridylmethyl)-3'-O-oleyl-5'-O-(monomethoxy)triethylene glycol-acetyl-thymidine; D004337:Drug Carriers; D053769:Nanocapsules; D009829:Oleic Acids; D011355:Prodrugs; D013936:Thymidine; D014529:Uridine