PVM/MA-shelled selol nanocapsules promote cell cycle arrest in A549 lung adenocarcinoma cells
JOURNAL OF NANOBIOTECHNOLOGY
Authors: de Souza, Ludmilla Regina; Muehlmann, Luis Alexandre; Costa dos Santos, Mayara Simonelly; Ganassin, Rayane; Simon-Vazquez, Rosana; Joanitti, Graziella Anselmo; Mosiniewicz-Szablewska, Ewa; Suchocki, Piotr; Morais, Paulo Cesar; Gonzalez-Fernandez, Africa; Azevedo, Ricardo Bentes; Bao, Sonia Nair
Abstract
Background: Selol is an oily mixture of selenitetriacylglycerides that was obtained as a semi-synthetic compound containing selenite. Selol is effective against cancerous cells and less toxic to normal cells compared with inorganic forms of selenite. However, Selol's hydrophobicity hinders its administration in vivo. Therefore, the present study aimed to produce a formulation of Selol nanocapsules (SPN) and to test its effectiveness against pulmonary adenocarcinoma cells (A549). Results: Nanocapsules were produced through an interfacial nanoprecipitation method. The polymer shell was composed of poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) copolymer. The obtained nanocapsules were monodisperse and stable. Both free Selol (S) and SPN reduced the viability of A549 cells, whereas S induced a greater reduction in non-tumor cell viability than SPN. The suppressor effect of SPN was primarily associated to the G2/M arrest of the cell cycle, as was corroborated by the down-regulations of the CCNB1 and CDC25C genes. Apoptosis and necrosis were induced by Selol in a discrete percentage of A549 cells. SPN also increased the production of reactive oxygen species, leading to oxidative cellular damage and to the overexpression of the GPX1, CYP1A1, BAX and BCL2 genes. Conclusions: This study presents a stable formulation of PVM/MA-shelled Selol nanocapsules and provides the first demonstration that Selol promotes G2/M arrest in cancerous cells.
Tuning Crystal Morphology of Succinic Acid Using a Polymer Additive
CRYSTAL GROWTH & DESIGN
Authors: Klapwijk, Anneke R.; Simone, Elena; Nagy, Zoltan K.; Wilson, Chick C.
Abstract
The effect of the triblock copolymer Pluronic P123 (PP123) on the growth of succinic acid crystals from aqueous solutions is reported at two batch process scales: 10 and 350 mL. The presence of small quantities of PP123 is shown to modify the crystal morphology from plate-like crystals to block-like crystals, in a fully reproducible manner. Increasing the quantity of polymer present, or the concentration of succinic acid used, produces needle-like crystals that are less favorable for processing. In-line process analytical tools (FBRM, PVM, and Raman) were implemented for the larger volume batch processes, allowing the crystallization to be monitored in real time. The effect of the polymer on the metastable zone width (MSZW) has also been determined in designing the crystallization experiments and is presented. In addition, the effect of the individual blocks of the copolymer, poly(ethylene glycol) and poly(propylene glycol), on the crystal morphology was examined, and these findings, together with face indexing and knowledge of the underlying crystal structure, have allowed a possible mechanism to be constructed for the interaction of the polymer with the crystal surface. This mechanism is supported by subsequent recrystallization experiments following washing of the block-like crystals with a nonpolar solvent.