M.A. Ruiz

Magnetite/poly(alkylcyanoacrylate) (core/shell) nanoparticles as 5-Fluorouracil delivery systems for active targeting.

In this article, a reproducible emulsion polymerization process is described to prepare core/shell colloidal nanospheres, loaded with 5-Fluorouracil, and consisting of a magnetic core (magnetite) and a biodegradable polymeric shell [poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate), or poly(octylcyanoacrylate)]. The heterogeneous structure of these carriers can confer them both the possibility of being used as drug delivery systems and the responsiveness to external magnetic fields, allowing an active drug targeting without a concurrent systemic distribution. Zeta potential determinations as a function of ionic strength showed that the surface behaviour of the core/shell particles is similar to that of pure cyanoacrylate particles. The first magnetization curve of both magnetite and magnetite/polymer particles demonstrated that the polymer shell reduces the magnetic responsiveness of the particles, but keeps unchanged their ferrimagnetic character. Two drug loading mechanisms were studied: absorption or entrapment in the polymeric network, and surface adsorption. We found that the acidity of the medium had significant effects on the drug absorption per unit mass of polymer, and needs to be controlled to avoid formation of macroaggregates and to reach significant 5-Fluorouracil absorption. The type of polymer and the drug concentration are also main factors determining the drug incorporation to the core/shell particles. 5-Fluorouracil release evaluations showed a biphasic profile affected by the type of polymeric shell, the type of drug incorporation and the amount of drug loaded.

Iron/ethylcellulose (core/shell) nanoplatform loaded with 5-fluorouracil for cancer targeting

Even though 5-fluorouracil has been demonstrated to display antitumor activity against a wide variety of cancers, high doses are needed to bring out the required therapeutic activity that could simultaneously lead to severe side effects. We hypothesized that the efficient delivery of 5-fluorouracil to tumors using a magnetic nanoplatform could reduce the dose required to obtain sufficient anticancer response. Thus, we have formulated a 5-fluorouracil-loaded magnetic nanomedicine consisting of a magnetic core (iron) and a biocompatible polymeric shell (ethylcellulose). These core/shell nanoparticles were synthesized by an emulsion solvent evaporation process, and 5-fluorouracil loading was assayed by surface incorporation onto the preformed nanocomposites, and by drug incorporation into the magnetic colloid. The contributions of both the surface and the polymeric network to the overall drug loading were investigated by means of optical absorbance and electrophoretic mobility determinations. 5-Fluorouracil entrapment into the polymeric matrix yielded a higher drug loading and a slower drug release profile as compared with drug adsorption. These preliminary results suggest the potential of this stimuli-sensitive drug carrier for cancer targeting.

Kollidon® SR colloidal particles as vehicles for oral morphine delivery in pain treatment

Due to the great importance of new therapeutic routes for morphine in pain treatment, several investigations are under development. In this way, the design of a liquid system for the oral administration of morphine would be of great help, especially in patients with difficulties in swallowing (children and elderly people). The systems studied in this work are kollidon SR microparticles, a biodegradable polymer classically used as excipient in the design of solid dosage forms, as vehicles for morphine. A detailed investigation of the capabilities of the polymer particles to load this drug at their surface is described. Electrophoretic mobility and optical absorbance determinations were used with this aim. The main factors determining the drug incorporation, after incubation of the microparticles in the morphine solutions, were the adsorption time, the type of electrolyte and its concentration, and the drug concentration. The optimum loading conditions were used to perform morphine release evaluations, finding that the release profiles were biphasic since the drug adsorbed was slowly released during 24h after an initial burst release phase.

Electrokinetic study of omeprazole drug in aqueous suspensions

Abstract Omeprazole is a antisecretory drug used against gastric ulcers. In this work, we investigate the electric surface characteristics of omeprazole by means of determinations of its electrophoretic mobility, μ e . The effects of pH and the concentration of different electrolytes on the mobility of the drug particles will be analysed. pH seems to be the main variable governing the surface charge and stability of the drug. Specific adsorption of ions is also important.

Stability of cellulose acetophthalate latex

Abstract The stability of cellulose acetophthalate latex (Aquateric™) was studied with differential scanning calorimetry, spectrophotometry, and scanning and transmission electron microscopy. We investigated the effects of pH, temperature and shaking on physicochemical properties of the latex particles. Stability of the polymer was most strongly affected by pH; hence, we conclude that the stability of this latex reaches a maximum at acid pH values, whereas stability is lost at neutral and alkaline pH.

Effect of amino acids on the stability properties of nitrofurantoin suspensions. Flocculation and redispersion compared with interaction energy curves

The influence of the addition of amino acids, lysine, alanine and glutamic acid on the properties of nitrofurantoin suspensions was investigated. Flocculation and redispersability was investigated, taking into account the electrical properties of the nitrofurantoin/solution interface.

Synthesis of a biodegradable magnetic nanomedicine based on the antitumor molecule tegafur.

The introduction of magnetic nanocarriers in chemotherapy aims to enhance the anticancer activity of antitumor molecules whereas keeping their toxicity to a very minimum. Magnetite/poly(hexylcyanoacrylate) (core/shell) nanoplatforms were synthesized by an emulsion/polymerization procedure. An exhaustive physicochemical characterization (including infrared spectrometry, electrophoresis, and thermodynamic analysis) suggested that the magnetite nuclei were embedded into a polymeric nanomatrix. The very good magnetic responsiveness of such core/shell nanoparticles was defined by the hysteresis cycle. To improve the intravenous delivery of tegafur to cancer, we investigated its incorporation into the nanoplatform. Compared to surface adsorption, drug entrapment into the polymeric shell yielded higher tegafur loading values, and a much slower release profile. A high frequency alternating magnetic gradient was used to elucidate the heating characteristics of the nanoparticles: a stable maximum temperature of 46 °C was successfully achieved within 32 min. Thus, we put forward that such kind of multifunctional nanomedicine hold very important characteristics (i.e., high drug loading, little burst release, hyperthermia, and magnetically targeted tegafur delivery), suggestive of its potential for combined antitumor therapy against cancer.