期刊
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
卷 98, 期 -, 页码 472-481出版社
ELSEVIER
DOI: 10.1016/j.msec.2018.11.051
关键词
Hyaluronic acid calcium complexes; Biodegradable injectable hydrogels; Sustained local delivery; Hydrophobic drug delivery; Cyclosporine A
资金
- Basic Science Research Programs through the National Research Foundation of Korea (NRF), Ministry of Education [2015R1C1A2A01052496, 2018R1D1A1A02047280, NRF-2018K1A4A3A01064257]
- National Research Foundation of Korea [2015R1C1A2A01052496, 2018R1D1A1A02047280] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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, H-1 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 mu m 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 degrees C. The hydrolytic degradation of the HA-Ca-Alg hydrogel was also examined at 37 degrees 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.
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