Synthesis and Physicochemical Characterization of Smart Magnetic Nanoparticles Containing Amoxicillin

Abstract

Objectives: Over the past years, magnetic temperature and pH-sensitive hydrogels were designed and developed as ‘‘smart’’ drug delivery systems. Temperature-responsive and pH-sensitive polymers have become increasingly attractive as carrier for the oral drug delivery systems. One of the most widely investigated temperature-sensitive polymers are poly (N-isopropyl acrylamide) (PNIPAAm) and related copolymers. Hydrogel nanoparticles (nanogels) have gained considerable attention in recent years as one of the most promising nanoparticulate drug delivery systems owing their unique potentials via combining the characteristics of hydrogel system such as extremely high water content with nanoparticle characteristics such as their very small size. The aim of this study is using magnetic NIPAAm-AA-HEM copolymers for site-specific drug delivery. Material and Methods: New magnetic cross-linked hydrogels nanocomposites based on poly(N-isopropylacrylamide) (PNIPAAm),poly (hydroxyethyl methacrylate)(HEM) and poly(acrylic acid) (AA), cross-linked with triethylenglycol dimethacrylate (TEGDM),were prepared and investigated for potential gastrointestinal drug delivery vehicles loaded with amoxicillin as the model drug. Cross-linked hydrogels were synthesized by simultaneous polymerization/crosslinking of PNIPAAm monomer in the presence of other comonomers and crosslinker (TEGDM). Two different type of emulsifier (PVA and Tween®20) were used to control the overall size of the hydrogel nanocomposite. Spectroscopic and thermal analyses such as infrared spectroscopy (FT-IR) were performed for hydrogel characterization. Equilibrium swelling studies were conducted for pH and temperature response behavior. Swelling studies were also carried out in simulated gastric fluid of pH=1.1 and simulated intestinal fluid of pH=7.4 to investigate possible site-specific drug delivery. Drug loading was carried out by adding predetermined amounts of amoxicillin and Fe3O4 after polymerization/crosslinking reactions. The in vitro release studies of the entrapped drug were carried out by placing the drug-loaded samples into buffered solution (with 1.1 pH and pH 7.4) at 37°C.The amount of released drug was measured spectrophotometrically at λ max=271 nm. Result and Discussion: It was found that the release behavior of the drug from these magnetic hydrogel- Fe3O4 nanocomposites was dependent on the pH of the medium and the type of emulsifier in the hydrogel. It was observed that amoxicillin release rate at pH=1.1 was higher than that at pH=7.4. Furthermore, the total release time of amoxicillin from cross-linked magnetic hydrogel- Fe3O4 nanocomposites to the buffered solutions with different pH values was found to be in the range 3-10 h which is consistent with gastrointestinal transit time of oral dosage forms in the human body. Consequently, cross-linked hydrogel- Fe3O4 nanocomposites developed in this study may serve as a potential device for the delivery of drugs in which the primary target is the stomach or the upper small intestine.