Preparation, characterization and in vitro evaluation of sterically stabilized liposome containing a naphthalenediimide derivative as anticancer agent. (August 2015)

• Record Type: Journal Article
• Authors: Parise, Amelia; Milelli, Andrea; Tumiatti, Vincenzo; Minarini, Anna; Neviani, Paolo; Zuccari, Guendalina
• Is Part Of: Drug delivery. Volume 22:Number 5(2015:Jul.)
• Page Start: 590
• Page End: 597
• Publication Date: 2015-08
• Subjects: Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2013.861042
• Languages: English
• ISSNs: 1071-7544

Abstract

<abstract> <title>Abstract</title> <p>The aim of this study was to incorporate a new naphthalenediimide derivative (AN169) with a promising anticancer activity into pegylated liposomes to an extent that allows its <italic>in vitro</italic> and <italic>in vivo</italic> testing without use of toxic solvent. AN169-loaded liposomes were prepared using the thin-film hydration method and characterized for size, polydispersity index, drug content and drug release. We examined their lyophilization ability in the presence of cryoprotectants (trehalose, sucrose and lysine) and the long-term stability of the lyophilized products stored at 4 °C for 3 and 6 months by particle size changes and drug leakage. AN169 was successfully loaded into liposomes with an entrapment efficiency of 87.3 ± 2.5%. The hydrodynamic diameter of these liposomes after sonication was ∼145 nm with a high degree of monodispersity. Trehalose was found to be superior to the other lyoprotectants. In particular, trehalose 1:10 lipid:cryoprotectant molar ratio may provide stable lyophilized liposomes with the conservation of physicochemical properties upon freeze-drying and long-term storage conditions. We also assessed their <italic>in vitro</italic> antitumor activity in human cancer cell lines (HTLA-230 neuroblastoma, Mel 3.0 melanoma, OVCAR-3 ovarian carcinoma and SV620 prostate cancer cells). However, only after 72 h incubation, loaded liposomes showed almost the same IC<sub>50</sub> as free AN169. In conclusion, we developed a stable lyophilized liposomal formulation for intravenous administration of AN169 as anticancer drug, with the advantage of avoiding the use of potentially toxic solubilizing agents for future <italic>in vivo</italic> experiments.</p> </abstract>