V. Gallardo

Synthesis and characterization of poly(ethyl-2-cyanoacrylate) nanoparticles with a magnetic core

A method is described to prepare composite colloidal nanoparticles, consisting of a magnetic core (magnetite) and a biodegradable polymeric shell (poly(ethyl-2-cyanoacrylate) or PE-2-CA). The method is based on the so-called anionic polymerization procedure, often used in the synthesis of PE-2-CA nanospheres designed for drug delivery. In the present work, the heterogeneous structure of the particles can confer both magnetic-field responsiveness and potential applicability as a drug carrier. In order to investigate to what extent this target is achieved, we compare the structure, chemical composition, and surface properties of the core/shell particles with those of both the nucleus and the coating material. This preliminary study shows that the synthetic new material displays an intermediate behavior between that of magnetite and PE-2-CA spheres. Thus, electrophoresis measurements as a function of pH and as a function of KNO3 concentration, show great similarity between the core/shell and pure polymer nanoparticles. A similar conclusion is reached when a surface thermodynamic study is performed on the three types of particles: the electron-donor component of the surface free energy of the solids is the quantity that appears to be most sensitive to the surface composition. The fact that PE-2-CA is close to being a non-polar material gives rise to a measurable decrease in the electron-donor component of the surface free energy of core/shell particles as compared to magnetite.

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.

Doxorubicin-Loaded Nanoparticles: New Advances in Breast Cancer Therapy

Doxorubicin, one of the most effective anticancer drugs currently known, is commonly used against breast cancer. However, its clinical use is restricted by dose-dependent toxicity (myelosuppression and cardiotoxicity), the emergence of multidrug resistance and its low specificity against cancer cells. Nanotechnology is a promising alternative to overcome these limitations in cancer therapy as it has been shown to reduce the systemic side-effects and increase the therapeutic effectiveness of drugs. Indeed, the numerous nanoparticle-based therapeutic systems developed in recent years have shown low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. Furthermore, the wide range of nanoparticle systems available may provide a solution to the different problems encountered during doxorubicin-based breast cancer treatment. Thus, a suitable nanoparticle system may transport active drugs to cancer cells using the pathophysiology of tumours, especially their enhanced permeability and retention effects, and the tumour microenvironment. In addition, active targeting strategies may allow doxorubicin to reach cancer cells using ligands or antibodies against selected tumour targets. Similarly, doxorubicin resistance may be overcome, or at least reduced, using nanoparticles that are not recognized by P-glycoprotein, one of the main mediators of multidrug resistance, thereby resulting in an increased intracellular concentration of drugs. This paper provides an overview of doxorubicin nanoplatform-based delivery systems and the principal advances obtained in breast cancer chemotherapy.

Study of carbonyl iron/poly(butylcyanoacrylate) (core/shell) particles as anticancer drug delivery systems Loading and release properties.

The aim of this study is to develop a detailed investigation of the capabilities of carbonyl iron/poly(butylcyanoacrylate) (core/shell) particles for the loading and release of 5-Fluorouracil and Ftorafur. The anionic polymerization procedure, used to obtain poly(alkylcyanoacrylate) nanoparticles for drug delivery, was followed in the synthesis of the composite particles, except that the polymerization medium was a carbonyl iron suspension. The influence of the two mechanisms of drug incorporation (entrapment in the polymeric network and surface adsorption) on the drug loading and release profiles were investigated by means of spectrophotometric and electrophoretic measurements. The optimum loading conditions were ascertained and used to perform drug release evaluations. Among the factors affecting drug loading, both pH and drug concentration were found to be the main determining ones. For both drugs, the release profile was found to be biphasic, since the drug adsorbed on the surface was released rather rapidly (close to 100% in 1h), whereas the drug incorporated in the polymer matrix required between 10 and 20h to be fully released. The kinetics of the drug release from the core/shell particles was mainly controlled by the pH of the release medium, the type of drug incorporation, and the amount of drug loaded.

Chitosan nanoparticles as a new delivery system for the chemotherapy agent tegafur

Background: Despite the very efficient antitumor activity of conventional chemotherapy, generally high doses of anticancer molecules must be administered to obtain the required therapeutic action, simultaneously leading to severe side effects. This is frequently a consequence of the development of multidrug resistance by cancer cells and of the poor pharmacokinetic profile of these agents. Objective: In Order to improve the antitumor effect of tegafur and overcome their important drawbacks, we have investigated its incorporation into a drug nanoplatform based on the biodegradable polymer chitosan. Materials and Methods: Two tegafur loading methods were studied: (i) absorption into the polymeric network (entrapment procedure); and (ii) surface deposition (adsorption procedure) in already formed chitosan nanoparticles. Results: Tegafur entrapment into the polymeric matrix has yielded higher drug loading values and a slower drug release profile, compared to single surface adsorption. The main factores determining the drug loading to chitosan were identified. Discussion and Conclusion: Such polymeric colloid present very interesting properties for efficient tegafur delivery to cancer.

Multilamellar liposomes of triamcinolone acetonide: preparation, stability, and characterization

The aim of this study was to assess and characterize the stability of multilamellar liposomes as a delivery vehicle for triamcinolone acetonide. A standardized preparation method for a liposomal delivery vehicle was developed, after varying composition and storage conditions, and assessing encapsulation efficiency and loss of active principle. The assessment of temperature as a factor in formula stability during storage showed that stability improved under refrigeration (4–6°C) (less early diffusion of active principle through the liposomal wall), in comparison with samples stored at room temperature. To improve stability, cholesterol was added to some formulae, which although resulting in a decrease in average encapsulation efficiency, mitigated subsequent losses of retained active principle (formulae 4, 5, and 6), in comparison with those without cholesterol (formulae 1, 2, and 3). This was evident both under refrigerated and room-temperature conditions. Finally, after testing the effects of adding an antioxidant and/or preservative to the formulae, a liposomal design was achieved with acceptable stability, vesicle dimensions, and encapsulation efficiency.

Preparation, Rheological Study, and Characterization of an Organogel as a System for Transdermal Release of Active Principles

The use of formulations containing Pluronic® gel as a vehicle and permeabilizing agent for transdermal preparations has increased in recent years. We prepared and compared two transdermal formulations for drug administration as an alternative to oral or parenteral administration. In formulations containing Pluronic® F127 gel or pluronic lecithin organogel (PLO), rheological, structural (transmission electron microscopy) and physicochemical characteristics were studied under different conditions of composition, temperature, and time from 24 hr to 3 months after preparation. Rheological studies at 20–25°C and at 4°C to study the influence of refrigeration on viscosity and pH showed that both formulas were thermoreversible. Unilamellar vesicles smaller than 1 μm in diameter were seen in the PLO formulation on TEM observation. The characteristics of these excipients may facilitate the application and may avoid the gastrointestinal tract and the first-pass effect.

Determination of the stability of omeprazole by means of differential scanning calorimetry

Differential scanning calorimetry was used to study the stability of omeprazole in two forms: granules and powder. The drug was subjected to light, elevated temperature (40 and 60°C) and different pH values. The greatest alterations in stability were caused by pH, followed by light.

Electric and adsorption properties of pharmaceutical polymers. Part I: Electrokinetics of Aquacoat

The characterization of the electrical surface properties of Aquacoat, a polymer latex of great interest in pharmaceutical sciences, is described. The technique used is electrophoresis. Analysis was carried out of the effect of pH, electrolyte and surfactant concentration on the electrophoretic mobility of the latex particles. Increasing the pH of the dispersion medium provokes a monotonous increase in the value of the negative mobility. The electrolytes LiCl, KCl and NaCl give rise to larger mobilities when their concentration in solution is increased up to ca. 10−3 M, and a similar behavior is found in the presence of Na2SO4. The effect of raising the concentration of CaCl2 is to decrease the absolute value of the mobility as a consequence of double layer compression. Sodium dodecyl sulphate seems to adsorb on the particle surface increasing its negative charge, but when its concentration is close to 10−3 M saturation of the surface appears to take place, and an approximately constant mobility is suggested by data, whatever the pH of the medium. Finally, the mobility variations with LaCl3 concentration indicate adsorption of the La3+ cation when it is hydrolyzed (pH≥5), whereas non-hydrolyzed lanthanum has little effect on the particle charge.

Measurement of dynamic surface tension to determine critical micellar concentration in lipophilic silicone surfactants

Silicone surfactants are becoming increasingly important in the pharmaceutical and cosmetic industry, because of their versatility, low cost, and technological advantages. The present study was designed to measure the critical micellar concentration of three non-ionic silicone surfactants, one water-soluble and two lipid-soluble. We measured surface tension with a technique based on drop geometry. Solubility and dispersibility in water were tested in the two lipophilic surfactants with visible and UV light spectrophotometry. The data obtained with all techniques showed a characteristic behavior of lipophilic silicone surfactants, which did not entirely conform to the definition of critical micellar concentration.