ABSTRACT
Innovative niosomes made up of α,ω-hexadecyl-bis-(1-aza-18-crown-6) (bola), Span 80® and cholesterol (2:5:2 molar ratio) are proposed as suitable delivery systems for the administration of 5-fluorouracil (5-FU), an antitumoral compound largely used in the treatment of breast cancer. The bola-niosomes, after sonication procedure, showed mean sizes of ~200 nm and a loading capacity of ~40% with respect to the amount of 5-FU added during the preparation. Similar findings were achieved with PEG-coated bola-niosomes (bola, Span 80(R), cholesterol, DSPE-mPEG2000, 2:5:2:0.1 molar ratio respectively). 5-FU-loaded PEG-coated and uncoated bola-niosomes were tested on MCF-7 and T47D cells. Both bola-niosome formulations provided an increase in the cytotoxic effect with respect to the free drug. Confocal laser scanning microscopy studies were carried out to evaluate both the extent and the time-dependent bola-niosome-cell interaction. In vivo experiments on MCF-7 xenograft tumor SCID mice models showed a more effective antitumoral activity of the PEGylated niosomal 5-FU at a concentration ten times lower (8 mg/kg) than that of the free solution of the drug (80 mg/kg) after a treatment of 30 days.
Subject(s)
Antineoplastic Agents/administration & dosage , Aza Compounds/chemistry , Crown Ethers/chemistry , Fluorouracil/administration & dosage , Polyethylene Glycols/chemistry , Surface-Active Agents/chemistry , Animals , Antineoplastic Agents/pharmacology , Capsules , Cell Transformation, Neoplastic , Chemical Phenomena , Fluorouracil/pharmacology , Humans , Liposomes , MCF-7 Cells , Mice , SolutionsABSTRACT
Bovine serum albumin nanospheres carrying cyclodextrin complexes for the delivery of progesterone were produced. Inclusion complexes composed of progesterone and hydroxypropyl-beta-cyclodextrin or dimethyl-beta-cyclodextrin were prepared by spray-drying or freeze-drying methods. Prog alone and its inclusion complexes were incorporated into bovine serum albumin nanospheres using a coacervation method and cross-linking with heating. The nanosphere suspensions were essicated by spray-drying or freeze-drying. The inclusion complexes and the nanospheres were characterized by Fourier Transform-Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC). Phase-solubility diagrams and stability constants were determined in distilled water at different temperatures (10, 25, and 37 degrees C). Size of nanospheres, their drug loading capacity and swelling ability were evaluated, as well as the in vitro controlled release profiles at pH 5.5 and 7.4.
