ABSTRACT
High-transition temperature liposomes with embedded coated magnetite nanoparticles were prepared using the thin lipid film hydration method in order to obtain magnetoliposomes not sensitive to temperature increase (at least up to 50°C). Accordingly, drug can be released from such magnetoliposomes using a low-level electromagnetic field as triggering agent, while no delivery would be obtained with temperature increase within the physiological acceptable range. The hypothesized release mechanism involves mechanical stress of the liposome membrane due to nanoparticles oscillations and it is investigated by means of a numerical model evaluated using multiphysics simulations. The carrier content was repetitively released by switching on and off a 20kHz, 60A/m magnetic field. The results indicated high reproducibility of cycle-to-cycle release induced by the magnetic-impelled motions driving to the destabilization of the bilayer rather than the liposome phase transition or the destruction of the liposome structure.
Subject(s)
Liposomes/chemistry , Magnetics , Magnetite Nanoparticles/chemistry , Transition Temperature , Algorithms , Calorimetry, Differential Scanning , Electric Conductivity , Hot Temperature , Lipids/chemistry , Magnetic Fields , Models, Chemical , Spectrophotometry , Static ElectricityABSTRACT
Diacerhein, a poorly water soluble antirheumatic prodrug, was spectroscopically characterized to form inclusion complexes with hydroxypropyl-ß-cyclodextrin (HPßCD) in both aqueous solution and in solid phase. Complexation with the hydrophilic carriers was used to improve the solubility and dissolution rate of the compound. The kinetics of the prodrug degradation to the active rhein in aqueous buffer solution were also investigated as a function of HPßCD concentration. The solid complexes prepared by different methods such as physical mixture, kneading, co-evaporation method and freeze dried method in 1:1M ratio, were characterized by DSC and FTIR. The dissolution profiles of solid complexes were determined and compared with diacerhein alone and their physical mixture, in the simulated intestinal fluid at 37°C. The accurate molecular spectroscopic characterization of diacerhein in the presence of different amounts of aqueous cyclodextrins was essential to determine the correct binding constants for the diacerhein/HPßCD system. The binding constants were also validated by UV spectrometry and HPLC procedure in order to compare the values from the different methods. Higuchi-Connors phase solubility method has proved not suitable when either the free or/and the complexed prodrug degrade in aqueous solution.
Subject(s)
Anthraquinones/chemistry , Anti-Inflammatory Agents/chemistry , Prodrugs/chemistry , Water/chemistry , beta-Cyclodextrins/chemistry , 2-Hydroxypropyl-beta-cyclodextrin , Anthraquinones/pharmacokinetics , Anti-Inflammatory Agents/pharmacokinetics , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Humans , Kinetics , Prodrugs/pharmacokinetics , beta-Cyclodextrins/pharmacokineticsABSTRACT
Recently, the use of liposomes loaded with magnetic nanoparticles (magnetoliposomes, (MLs)) has been intensely growing as a new drug delivery system. With the use of alternating magnetic fields, it is possible to remotely control the delivery of a drug or any other macromolecule loaded inside the MLs. In this experiment, the release of a fluorescent dye from MLs is achieved through an alternating magnetic field of 20 kHz and amplitude below 100 A/m, and without a macroscopic temperature increase.
