دانلود رایگان ترجمه مقاله میکرواسفرهای پکتین/TiO2 کووالانسی برای رهایش دارو (نشریه الزویر ۲۰۱۴)

میکرواسفرهای پکتین/TiO2 کووالانسی و دارای نانوذرات Fe3O4 برای رهایش دارو با تنظیم میدان مغناطیسی

Covalent TiO2/pectin microspheres with Fe3O4 nanoparticles for magnetic field-modulated drug delivery

Abstract

Covalent TiO2-co-pectin microspheres containing Fe3O4 nanoparticles were developed through an ultrasound-induced crosslinking/polymerization reaction between the glycidyl methacrylate from vinyl groups in TiO2 and in pectin. ζ-potentials became less negative in the nanostructured microspheres, caused by the presence of both inorganic particles in the negatively charged pectin. The nanostructured pectin microspheres showed an amoxicillin release rate slower than that of pure pectin microspheres. The proposed microspheres were found to be a sustained release system of amoxicillin in the acid medium. Furthermore, the antibiotic release may be modulated by exposition of the microspheres to a remote magnetic field. In practical terms, the nanostructured microspheres could deliver a larger proportion of their initial load to specific site of action. The cytotoxic concentrations for 50% of VERO cells (CC50), calculated as the concentration required to reduce cell viability by 50% after 72 h of incubation, for pectin-only microspheres and nanostructured pectin microspheres were 217.7 ± ۶٫۵ and 121.5 ± ۴٫۹ μg mL−۱, respectively. The obtained CC50 values indicated acceptable cytotoxic levels for an incubation period of 72 h, showing that the pectin microspheres have a great pharmacological potential for uses in biological environments, even after the introduction of both Fe3O4 and TiO2.

۱ Introduction

In the last years, smart (or intelligent) release systems (also called advanced materials) have been the target of important scientific investigations [1–۵], owing to their specific properties of being sensitive to external stimuli, such as temperature, pH and magnetic field. Drug delivery systems based on nanoparticles sensitive to a remotely applied magnetic field appear on the top of the (bio)technological innovations, because the magnetic field, if used in a therapeutic level, does not affect biological tissues.

Magnetite (Fe3O4) is a type of magnetic particle that has been the target of important studies on biomedicine because of its non-toxicity, high level of accumulation in tissues, interruption of magnetization whenthemagneticfieldis removed, andbiocompatibility due to high affinity for water which allows to interact with biological species [6–۸]. The combination of Fe3O4 with naturally occurring materials to produce a smart drug delivery system for use in pharmaceutical formulation is an innovative concept from a biotechnological point of view.

Pectin is an example of naturally occurring material that has received considerable attention in biomedicine [9,10]. The great advantage of using pectin in the development of micro and/or nanoparticles for drug delivery is based on its appealing properties such as biodegradability, controllable biologic activity, and flexible chains that allow the modulation of the polysaccharide to a specific shape. In this connection, pectin is an appropriate material for use in pharmaceuticalformulations [11,12]. This polysaccharide has been studied to act as a polymer biodevice for the treatment of some types of cancer that affect specific regions of the gastrointestinal tract (GI), for example, the colon. This is possible because pectin resists the drastic variations of the physiologic pH throughout GI, which assures the integrity of its polymer structure [13–۱۵]. Although the majority of the reports on pectin-based drug delivery systems have been focused on the treatment of GI diseases. some studies have shown the use of this polysaccharide in mucosa, owing to its mucoadhesive properties [16–۱۹]. However, the high solubility of pectin in water limits its application in a physiological medium, which can contribute to a premature release of the active principle. Chemical modification of pectin by the introduction of hydrophobic groups has been proposed to reduce its solubility. The incorporation of vinyl groups derived from glycidyl methacrylate (GMA)topolysaccharides is aprominentmodificationstrategy [20].

The focus of this work was on developing a smart biodevice based on magnetic pectin microspheres that shows a sustained release profile in a specific site in which the drug plays a role as a local therapeutic agent. The concept of such a device may be based on a tortuosity effect that sustains the release of the drug. This behavior is the result ofthe disposition of nanoparticles within the polymer device. A way of doing this is to incorporate inorganic nanoparticles to biodevice (pectin microspheres). This new material could be obtained by a pectin microsphere-nanostructuring approach using Fe3O4 as magnetic particle, and titanium (TiO2) as an inorganic crosslinker. Such architecture could show a versatile release profile. The release of the drug could be sustained for a longer time, and also controlled remotely. Furthermore, the introduction of TiO2 as a crosslinker for modified pectin could produce consistent microspheres. To obtain microspheres, a covalent approach using chemically modified TiO2 was developed. This process consisted of inserting vinyl radical onto TiO2 structure for further radical reaction with vinylated pectin.

The proposed biodevice is addressed to the treatment of Helicobacter pylori(H. pylori)-associated ulcers that affectthe mucosa of the stomach. Amoxicillin was used in the studies of release because it inhibits the growth of H. pylori. This antibiotic is effective against H. pylori in the in vitro therapy in which low doses of the drug are required over the oral administration. However, to obtain the same efficiency in the in vivo therapy, higher doses of the antibiotic are required, owing to the high rate of emptying of food (or contents) from the stomach into intestine that limits the release and absorption of a given drug. The magnetic pectin microspheres are a new architecture that shows a great potential for future tests in the treatment of gastric ulcers.