Injectable thermosensitive hydrogels have been widely investigated for drug delivery systems. Chitosan (CH) is one of the most abundant natural polymers, and its biocompatibility and biodegradability make it a favorable polymer for thermosensitive hydrogel formation. The addition of nanoparticles can improve its drug release behavior, remote actuation capability, and biological interactions. Carbon nanotubes (CNTs) have been studied for the use in drug delivery systems, and they can act as drug delivery vehicles to improve the delivery of different types of therapeutic agents. In this work, carbon nanotubes were incorporated into a thermosensitive and injectable hydrogel formed by chitosan and β-glycerophosphate (β-GP) (CH−β-GP–CNTs). The hybrid hydrogels loaded with methotrexate (MTX) were liquid at room temperature and became a solidified gel at body temperature. A number of tests including scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction were utilized to characterize the MTX-loaded CH−β-GP–CNT hybrid hydrogels. The cell viability (alamarBlue) assay showed that hydrogels containing CNT (0.1%) were not toxic to the 3T3 cells. In vitro MTX release study revealed that CNT-containing hydrogels (with 0.1% CNT) demonstrated a decreased MTX releasing rate compared with control hydrogels without CNT. The cultured MCF-7 breast cancer cells were used to evaluate the efficacy of CH−β-GP–CNT hybrid hydrogels delivering MTX on the control of tumor cell growth. Results demonstrated that CNT (0.1%) in the hydrogel enhanced the MTX antitumor function. Our study indicates that a thermosensitive CH−β-GP–CNT hybrid hydrogel can be used as a potential breast cancer therapy system for controlled delivery of MTX.

Chitosan has the ability to make injectable thermosensitive hydrogels which has been highly investigated for drug delivery applications. The addition of nanoparticles is one way to increase the mechanical strength of thermosensitive chitosan hydrogel and subsequently and control the burst release of drug. Graphene nanoparticles have shown unique mechanical, optical and electrical properties which can be exploited for biomedical applications, especially in drug delivery. This study, have focused on the mechanical properties of a thermosensitive and injectable hybrid chitosan hydrogel incorporated with graphene nanoparticles. Scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and X-ray diffraction (XRD) have been used for morphological and chemical characterization of graphene infused chitosan hydrogels. The cell viability and cytotoxicity of graphene-contained hydrogels were analyzed using the alamarBlue technique. In-vitro methotrexate (MTX) release was investigated from MTX-loaded hybrid hydrogels as well. As a last step, to evaluate their efficiency as a cancer treatment delivery system, an in vitro anti-tumor test was also carried out using MCF-7 breast cancer cell lines. Results confirmed that a thermosensitive chitosan-graphene hybrid hydrogel can be used as a potential breast cancer therapy system for controlled delivery of methotrexate. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2381-2390, 2017.

Targeted drug delivery systems have been shown to be promising alternative for the conventional drug delivery methods. Among numerous nanocarriers developed for therapeutic applications, iron oxide magnetic nanoparticles have attracted considerable attention. Fe3O4 (magnetite) is one of the most commonly used iron oxide in biomedical applications due to its biocompatibility and can be easily produced in research and industrial laboratories. The core/shell structure of magnetic nanoparticles allows the surface coating to avoid their agglomeration. Moreover, coating of Fe3O4 nanoparticles provide functional groups and consequently make the bioconjugation to the therapeutic agents. Coating magnetic nanoparticles with a biopolymer will also increase biocompatibility. Coating magnetic nanoparticles with a biopolymer will also increase biocompatibility. Chitosan can easily conjugate to the surface of magnetic nanoparticles and provide amine and hydroxyl groups for the further conjugation of the therapeutic drug. In this study, Fe3O4 magnetic nanoparticles were fabricated and were coated with chitosan via in-situ method. Prepared chitosan coated magnetic nanoparticles then were loaded with methotrexate (anti-cancer drug) through adsorption. The size and morphology of synthesized magnetic nanoparticles were evaluated using Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The chemical structure of bare and chitosan coated magnetic nanoparticles was analyzed by Fourier Transforms Infrared (FTIR). Methotrexate loading efficiency of chitosan coated nanoparticles was also evaluated. Cytotoxicity of nanoparticles was also studied in-vitro. The results confirmed the surface coating with chitosan and methotrexate loading. The synthesize chitosan coated magnetic nanoparticles showed promising application for cancer treatment.

Hydrogels are the promising classes of polymeric drug delivery systems with the controlled release rates. Among them, injectable thermosensitive hydrogels with transition temperature around the body temperature have been wildly considered. Chitosan is one of the most abundant natural polymers, and its biocompatibility and biodegradability makes it a favorable thermosensitive hydrogel that has been attracted much attention in biomedical field worldwide. In this work, a thermosensitive and injectable hydrogel was prepared using chitosan and β-glycerophosphate (β-GP) incorporated with an antibacterial drug (gentamycin). This drug loaded hydrogel is liquid at room temperature, and becomes more solidified gel when heated to the body temperature. Adding β-GP into chitosan and drug molecules and heating the overall solution makes the whole homogenous liquid into gel through a 3D network formation. The gelation time was found to be a function of temperature and concentration of β-GP. This thermosensitive chitosan based hydrogel system was characterized using FTIR and visual observation to determine the chemical structure and morphology. The results confirmed that chitosan/(β-GP) hydrogels could be a promising controlled-release drug delivery system for many deadly diseases.

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