Researchers at the Shanghai Jiao Tong University, in China, synthesized a gene delivery system that effectively to treat endometriosis. Their work, detailed in the study “Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation,” was published in the International Journal of Nanomedicine.
Endometriosis is a condition characterized by the growth of the uterus lining tissue outside the uterus, causing chronic pelvic pain and infertility in women. The mechanisms and pathophysiology of endometriosis, however, are still unclear.
Current clinical treatment includes the surgical removal of endometriotic tissue and uterus, or drugs that regulate the production of the cyclic ovarian hormones. But drugs — like progesterone, gonadotropin-releasing hormone, danazol, angiogenesis disruption, and antitumor necrosis factor-alpha inhibitors — are often associated with a number of adverse effects that limit their long-term use. Identifying new treatment candidates is of importance.
Researchers synthesized a novel polymeric nanoparticle gene delivery system based on polyethylenimine-grafted chitosan oligosaccharide (CSO-PEI), coupled with hyaluronic acid (HA) and small interfering RNA (siRNA) to form (CSO-PEI/siRNA) HA drug particles. Importantly, HA is widely distributed throughout connective, epithelial, and neural tissues.
While the results from particle size analysis suggested that the addition of HA to CSO-PEI/siRNA did not influence the particle size, fluorescence data revealed that accumulation of (CSO-PEI/siRNA) HA in the tissue was more noticeable than CSO-PEI/siRNA. This is induced by the particular binding of HA to an antigen called CD44, involved in many cellular functions, including interaction, adhesion, and migration of cells.
Other results showed that the (CSO-PEI/siRNA) HA nanoparticles significantly reduced endometriotic lesion sizes, and administration of (CSO-PEI/siRNA) HA to a rat model of endometriosis reduced expression of CD44 in their epithelial cells.
Finally, electron microscopy studies depicted no obvious toxic effect of (CSO-PEI/siRNA) HA on the reproductive organs. “(CSO-PEI/siRNA)HA gene delivery system can be used as an effective method for the treatment of endometriosis,” the authors wrote.
“As for the effect, the dose of (CSO-PEI/siRNA)HA might be a key part influencing the result. In contrast, the nanoparticle improves the holding of siRNA in the [animal] organ and performs significant knockdown in the target gene expression for at least 10 days using a single dose of intravenous injection. In this study, only one dose of (CSO-PEI/siRNA)HA was used, and more doses and plurality of time points need to be studied in the next study,” they concluded.
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