Sodium alginate/podophyllotoxin drug delivery system: preparation, release and anti-colon cancer effects

doi:10.3969/j.issn.2095-4344.0917

Abstract

Abstract:

BACKGROUND: Podophyllotoxin has the function of inhibiting cancer cell proliferation, antiviral and pest resistance, but its use alone causes great adverse reactions and has low bioavailability.

OBJECTIVE: To prepare sodium alginate/podophyllotoxin gel beads aiming to achieve the control release or targeted drug delivery that can improve effectiveness and reduce biotoxicity and adverse events.

METHODS: External ion gel preparation of sodium alginate/podophyllotoxin gel beads was performed. Drug load efficiency of the gel beads with podophyllotoxin mass concentrations of 25, 50, and 75 g/L was detected, and swelling and release performance of the gel beads at different pH values (pH=2.1, 4.6, 7.4) was also measured. Colon cancer cells SW480 and intestinal epithelial cells NCM460 were cultured in the medium containing 5, 10, 20, 40 mg/L sodium alginate/podophyllotoxin gel beads, sodium alginate or podophyllotoxin alone. After 48 hours of culture, survival rate of NDM460 cells and inhibition rate of SW480 cells were detected.

RESULTS AND CONCLUSION: The drug loading rate of the gel beads was 8.97%, 17.02% and 19.16% respectively, when the mass concentration of podophyllotoxin was 25, 50 and 75 g/L. When the mass concentration of podophyllotoxin was 25, 50 and 75 g/L, the gel beads were almost insoluble in the pH=2.1 and pH=4.6 environment. In the environment of pH=7.4, the swelling rate of gel beads increased with the increase of the mass concentration of podophyllotoxin. In the environment of pH=7.4, there was a slow release of podophyllotoxin, (69.5±9.1)%, from the gel beads in 24 hours. In the environment of pH=2.1 and 4.6, only (2.0±0.2)% and (2.1±0.6)% podophyllotoxin was released from the gel beads in 24 hours, respectively. With the increase of drug mass concentration, the survival rate of NCM460 cells in each group declined gradually. Sodium alginate had no cytotoxicity, but podophyllotoxin exhibited obvious cytotoxicity. Moreover, the gel beads could reduce the cytotoxicity of podophyllotoxin. With the increase of drug mass concentration, the inhibition rate of SW480 cells in each group increased gradually, and the inhibitory effect of the gel beads was stronger than that of sodium alginate and podophyllotoxin. These experimental findings indicate that the sodium alginate/podophyllotoxin gel bead is a promising pH sensitive slow-release colorectal cancer drug delivery system.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Podophyllotoxin, Colonic Neoplasms, Delayed-Action Preparations, Tissue Engineering

CLC Number:

R318

Wang Jiang, Wang Qing-feng, Jiang Yi-xin, Chen Na, Chu Zheng. Sodium alginate/podophyllotoxin drug delivery system: preparation, release and anti-colon cancer effects[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(22): 3498-3505.

Figures/Tables 9

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