Biodegradable and injectable hydrogels as an immunosuppressive drug delivery system
| Autor: | Han-Sem Kim, Kwangmi Kim, Jisu Yang, Ueon Sang Shin |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Materials science
Alginates medicine.medical_treatment Proton Magnetic Resonance Spectroscopy T-Lymphocytes chemistry.chemical_element Bioengineering Biocompatible Materials 02 engineering and technology Calcium 010402 general chemistry 01 natural sciences Injections Biomaterials chemistry.chemical_compound Drug Delivery Systems In vivo Hyaluronic acid Spectroscopy Fourier Transform Infrared medicine Animals Hyaluronic Acid Cell Proliferation Viscosity Hydrogels 021001 nanoscience & nanotechnology In vitro 0104 chemical sciences Mice Inbred C57BL Immunosuppressive drug chemistry Mechanics of Materials Drug delivery Self-healing hydrogels Thermogravimetry Systemic administration Biophysics Cyclosporine Interleukin-2 Female 0210 nano-technology Immunosuppressive Agents |
| Zdroj: | Materials scienceengineering. C, Materials for biological applications. 98 |
| ISSN: | 1873-0191 |
| Popis: | Cyclosporine A (CsA) is an extremely hydrophobic immunosuppressive drug, whose systemic administration to suppress the activity of T cells and T cell-based immune responses is frequently associated with a number of adverse drug reactions. Local delivery of CsA focused on a specific target organ has been proposed as a possible solution to this problem. In this study, we developed biodegradable sol-gel drug delivery systems, consisting of HA-Ca-Alg hydrogels combining hyaluronic acid calcium complex (HA-Ca) and sodium alginate (Alg-Na) components, for the local sustained delivery of CsA. A HA-Ca complex with very high degree of substitution was prepared by the acid-base reaction of hyaluronic acid and calcium acetate. The gelation was completed within about 2–45 min without external addition of calcium salts such as CaSO4 and CaCl2, indicating the high potential of the present hydrogel systems for drug delivery by injection in vivo. The HA-Ca system was characterized by high-resolution inductively coupled plasma-optical emission spectroscopy, 1H NMR, FT-IR, and thermogravimetric analysis methods. Moreover, the scanning electron microscopy analysis of the HA-Ca-Alg hydrogels showed an irregular porous morphology, with interconnected pores of 50–300 μm width. The sol-gel transition and the maximum viscosity (about 10,000 cP) of the HA-Ca-Alg hydrogels were characterized by examining the time evolution of the viscosity at 37 °C. The hydrolytic degradation of the HA-Ca-Alg hydrogel was also examined at 37 °C. CsA-encapsulated HA-Ca-Alg hydrogels exhibited sustained in vitro release of CsA over 14 days, which was confirmed through in vitro measurements of the activity of murine T cells over 2 weeks. These results show that the present injectable HA-Ca-Alg hydrogels can be used effectively for the sustained delivery of extremely hydrophobic immunosuppressive drugs, including CsA. |
| Databáze: | OpenAIRE |
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