ABSTRACT
The objective of this study was to develop pH-responsive silica nanoparticles by imidazole-based ionic liquid for controlled release of methotrexate. In this article, we synthesized pH-responsive cationic silica nanoparticles by graft copolymerization of vinyl functionalized silica nanoparticles and methacrylic acid (MAA) monomer. Imidazole-based ionic liquid (Im-IL) was verified by (1)HNMR and Fourier-transform infrared (FTIR) spectroscopy. The synthesized functionalized silica particles were characterized and confirmed by various technologies including the scanning electron microscopy (SEM), the infrared spectroscopy (IR) and the thermogravimetric analysis (TGA). SEM results reveal the uniformity in size/shape of silica particles. This nanosystem is modified for targeted delivery of an anticancer agent methotrexate. The nanocomposite-MTX complex was formed at physiological pH (7.4) due to the electrostatic interactions between anionic carboxylic group of MTX molecules and cationic rings in carrier, while, the release of which can be achieved through the cleavage of the nanocomposite-MTX complex by protonation of carboxyl groups in the MTX segment that are sensitive to variations in external pH at weak acidic conditions. FT-IR spectroscopy showed the presence of light interactions between the silicate silanols and the drug. MCF7 cells were incubated with the MTX-free nanocomposite and MTX-loaded nanocomposite at various concentrations for 24, 48 and 72 h, and the data showed that the nanocomposites themselves did not affect the growth of MCF7 cells. Antitumor activity of the MTX-loaded nanocomposites against the cells was kept over the whole experiment process. The results showed that the MTX could be released from the fibers without losing cytotoxicity.
Subject(s)
Antimetabolites, Antineoplastic/chemistry , Biocompatible Materials , Drug Carriers , Methotrexate/chemistry , Nanocomposites , Polymethacrylic Acids/chemical synthesis , Silicon Dioxide/chemical synthesis , Antimetabolites, Antineoplastic/pharmacology , Cell Proliferation/drug effects , Cell Survival/drug effects , Chemistry, Pharmaceutical , Delayed-Action Preparations , Dose-Response Relationship, Drug , Humans , Hydrogen-Ion Concentration , Imidazoles/chemistry , MCF-7 Cells , Methotrexate/pharmacology , Microscopy, Electron, Scanning , Nanotechnology , Polymethacrylic Acids/toxicity , Proton Magnetic Resonance Spectroscopy , Silicon Dioxide/toxicity , Solubility , Spectroscopy, Fourier Transform Infrared , Technology, Pharmaceutical/methods , Thermogravimetry , Time FactorsABSTRACT
pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic peptides, proteins, and drugs, due to their ability to respond to environmental pH changes. New pH-sensitive glycopolymers have been developed by free-radical polymerization of methacrylic acid and 6-acryloyl-glucose-1, 2, 3, 4-tetraacetate, using 1, 6-hexandiol diacrylate and 1, 6-hexandiol propoxylate diacrylate as cross-linking agents. The hydrogels were characterized by differential scanning calorimetry and FTIR. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). A model drug, olsalazine [3, 3'-azobis (6-hydroxy benzoic acid)] as an azo derivative of 5-aminosalicylic acid, was entrapped in these gels and the in vitro release profiles were established separately in both enzyme-free SGF and SIF. The drug-release profiles indicated that the amount of drug released depended on the degree of swelling. The hydrogels containing polar propoxylate groups were hydrolyzed rather easily.
Subject(s)
Colon/metabolism , Polymers/chemistry , Aminosalicylic Acids/administration & dosage , Aminosalicylic Acids/chemistry , Azo Compounds/chemistry , Calorimetry, Differential Scanning , Cross-Linking Reagents , Drug Delivery Systems , Free Radicals , Hydrogels , Hydrogen-Ion Concentration , Hydrolysis , Mesalamine/administration & dosage , Mesalamine/chemistry , Spectroscopy, Fourier Transform Infrared , ThermodynamicsABSTRACT
pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic peptides, proteins and drugs, due to their ability to respond to environmental pH changes. Terephthalic acid was covalently linked with 2-hydroxyethyl methacrylate (HEMA), abbreviated as cross-linking agent (CA). Acryloyl ester of 5-[4-(hydroxy phenyl) azo] salicylic acid (HPAS) as an azo derivative of 5-amino salicylic acid (5-ASA) was prepared under mild conditions. The HPAS was covalently linked with acryloyl chloride, abbreviated as APAS. Free radical cross-linking copolymerization of polymerizable azo derivative of 5-ASA (APAS) and methacrylic acid (MAA) in two different molar ratios, with the various ratios CA as cross-linking agent were carried out with using 2, 2'-azobisisobutyronitrile (AIBN) as initiator at the temperature range 60-70 degrees C. The composition of the cross-linked three-dimensional polymers was determined by FTIR spectroscopy. Glass transition temperature (Tg) of the network polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 7.4 and pH 1) at 37 degrees C. The effect of copolymer composition on the hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4) at 37 degrees C. Monitoring of the hydrolysis process by HPLC and UV spectroscopy shows that the azo prodrug (HPAS) was released by hydrolysis of the ester bond located between the HPAS and the polymer chain. The drug-release profiles indicate that amount drug release dependent on the content of MAA groups and crosslinking.
