Synthesis and characterization of xylan-coated magnetite microparticles

Abstract

This work evaluates an experimental set-up to coat superparamagnetic particles in order to protect them from gastric dissolution. First, magnetic particles were produced by coprecipitation of iron salts in alkaline medium. Afterwards, an emulsification/cross-linking reaction was carried out in order to produce magnetic polymeric particles. The sample characterization was performed by X-ray powder diffraction, laser scattering particle size analysis, optical microscopy, thermogravimetric analysis and vibrating sample magnetometry. In vitro dissolution tests at gastric pH were evaluated for both magnetic particles and magnetic polymeric particles. The characterization data have demonstrated the feasibility of the presented method to coat, and protect magnetite particles from gastric dissolution. Such systems may be very promising for oral administration.

Introduction

Magnetite particles have been proposed for oral use as magnetic resonance contrast agents and magnetic markers for monitoring gastrointestinal motility (Briggs et al., 1997, Ferreira et al., 2004). Magnetic resonance imaging (MRI) is a non-invasive technique which can provide cross-sectional images from inside solid materials and living organisms (Richardson et al., 2005). MRI has several inherent advantages, such as the lack of radiation exposure, excellent soft tissue contrast, and direct multiplanar capabilities (Kim and Ha, 2003). Advances in MRI, including the implementation of high-performance gradients and the availability of oral contrast agents, have led to an increasing use of MRI in the evaluation of the intestine (Lauenstein et al., 2003), markedly using magnetite particles (Briggs et al., 1997). Magnetite particles were also suggested as tracers to study the gastrointestinal motility. In fact, such magnetic measurement may be a promising tool in order to evaluate the dynamics of the gastrointestinal tract by monitoring ingested magnetic tracers. Once ingested, the magnetic tracers endow the gastrointestinal tract with a strong magnetic signal. Changes in magnetic signal would be caused by changes in magnetic orientation or volume within the organ due to its motor activity (Ferreira et al., 2004).

Despite the promising properties, magnetite particles dissolve in acid media. The rate of dissolution of oxides is known to increase with increasing hydrogen ion concentration (Schindler, 1991). Gastric juice has an approximate pH of 1, and the normal transit time in the stomach is 2 h (Paulev, 1999–2000; Sinha and Kumria, 2002). The gastric secretions include pepsin, mucus, and hydrochloric acid (HCl) (Paulev, 1999–2000). Therefore, magnetite particle dissolution may take place during the period in which particles pass through the stomach. Such possible particle loss could reduce the signal for MRI or for monitoring gastrointestinal motility, depleting the efficiency of the system.

Regarding pharmaceutical technology, protecting compounds from gastric environment is a key issue. In fact, many approaches have been proposed, namely coating with pH-sensitive polymers, time-dependent delivery systems, and the use of biodegradable polymers (Sinha and Kumria, 2001). Concerning pH-dependent systems, they exploit the fact that the pH of the human gastrointestinal tract increases progressively from the stomach (pH 1–2) to the intestine (pH 6–8). The polymers used to design such systems should be able to withstand the lower pH values of the stomach in order to protect the compound from the gastric fluid (Chourasia and Jain, 2003). The time-dependent formulations are designed to resist the release of the drug in the stomach with an additional non-disintegration or lag phase. Intestinal release is enabled, and protection from gastric environment is provided (Sinha and Kumria, 2001). The other strategy relies on the resistance of some polysaccharides to the digestive actions of gastrointestinal enzymes. The matrices of polysaccharides are assumed to remain intact in the physiological environment of stomach and small intestine. Once they reach the colon, bacterial polysaccharidases come into play, and degradation of the matrices takes place. Such group of polysaccharides is comprised of amylase, chitosan, pectin, dextran, inulin, chondoitrin, xylan, etc. These polymers present a large number of derivatizable groups, a wide range of molecular weights, low toxicity, biodegradability, and high stability (Chourasia and Jain, 2003). Because of the presence of biodegradable enzymes only in the colon, such systems seem to be more suitable with regard to selectivity as compared to the other approaches (Sinha and Kumria, 2001).

Among the colon-degradable polymer cited above, xylan is a very promising one. In fact, it is the most common hemicellulose, and represents more than 60% of the polysaccharides existing in the cell walls of corn cobs (Ebringerova et al., 1992). It is considered the second most abundant biopolymer in the plant kingdom. Its chemical structure is mainly composed of d-glucuronic acid, l-arabinose and d-xylose in the approximate ratio of 2:7:19 (Ebringerova et al., 1994). The aim of this work was to develop xylan-coated magnetic microparticles in order to protect magnetite from gastric dissolution.