Abstract
Background:
Secondary upper limb lymphedema commonly occurs after breast cancer surgery, for which treatment is limited. 9-cis-retinoic acid (9-cisRA) has been demonstrated to increase lymphangiogenesis without enhancing tumor metastasis but has disadvantages of poor water solubility, ready decomposition in light, instability to heat, and a short half-life.
Methods:
Based on this, 9-cisRA-Lip with a particle size of roughly 143 nm and high dispersibility was prepared by thin-film dispersion method and verified by Malvern Laser Particle Size Analyzer and electron microscopy.
Results:
In vitro, 9-cisRA-Lip demonstrated good biosafety and tumor safety, promoting the proliferation of L929 cells while having no effect on 4T1 and Human Umbilical Vein Endothelial (HUVEC) cells. Compared with 9-cisRA, 9-cisRA-Lip was more effective at stimulating mouse lymphatic endothelial cell (SVEC4–10) migration, proliferation, and tube formation. In vivo, 9-cisRA-Lip-Gel showed good slow release effect. Mice treated with 9-cisRA-Lip-Gel one-time local injection had considerably less tail edema than the control group from day 9 to day 39 postsurgery (p < 0.05). This may be attributed to the greater capacity of 9-cisRA-Lip to enhance the phosphorylation of FGFR3 (Fibroblast Growth Factor Receptor 3) at Tyr 724.
Conclusions:
9-cisRA-Lip-Gel presents a potential treatment option for lymphedema following surgery.
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