Nanomedicine for Uterine Leiomyoma Therapy

Background Statins are 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors primarily used for treatment of hyperlipidemia. Recently, they have been shown to inhibit proliferation of uterine fibroid cells and inhibit tumor growth in fibroid animal models. Objectives To examine the association between statin use and the risk of uterine fibroids and fibroid-related symptoms in a nationally representative sample of commercially insured women diagnosed with hyperlipidemia. Study Design We performed a nested case-control study of more than 190,000 women enrolled in one of the nation’s largest commercial health insurance programs. From a cohort of females aged 18–65 years old diagnosed with hyperlipidemia between January 2004 and March 2011, we identified 47,713 cases (women diagnosed with uterine fibroids)143,139 controls (women without uterine fibroids) matched at a 1:3 ratio on event/index date (month and year) and age (± 1 year). We used conditional and unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for the risk of uterine fibroids and fibroid-related symptoms associated with prior use of statins. Results Exposure to statins within 2 years before the event/index date was associated with a decreased risk of uterine fibroids (OR of 0.85, 95% CI 0.83–0.87). In a separate sub-analysis restricted to cases, statin users had a lower likelihood of having menorrhagia (OR 0.88, 95% CI 0.84–0.91), anemia (OR 0.84, 95% CI 0.79–0.88), or pelvic pain (OR 0.85, 95% CI 0.81–0.91) and of undergoing myomectomy (OR 0.76, 95% CI 0.66–0.87) compared to nonusers. Conclusion The use of statins was associated with a lower risk of uterine fibroids and fibroid-related symptoms. Further studies, including randomized controlled trials, may be warranted.

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“…1, 38 Therefore, there may be room for even more effective targeted delivery technologies, eg, nanotechnology. 39–41 …”

Section: Commentmentioning

confidence: 99%

Statin use and uterine fibroid risk in hyperlipidemia patients: a nested case-control study

Borahay

Fang

Baillargeon

et al. 2016

American Journal of Obstetrics and Gynecology

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“…These endocrine disruptions may have profound effects on the functionality of the cardiovascular system and associated vascular reactivity of the reproductive system (Ruehlmann et al, 1998). While therapeutic applications of nanomaterials on the uterus are under investigation (Ali et al, 2013), there are currently no studies that have evaluated the toxicokinetics of ENM exposure on uterine microvascular function.…”

Section: Introductionmentioning

confidence: 99%

Microvascular and mitochondrial dysfunction in the female F1 generation after gestational TiO₂nanoparticle exposure

Stapleton

Nichols

et al. 2015

Nanotoxicology

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Due to the ongoing evolution of nanotechnology, there is a growing need to assess the toxicological outcomes in under-studied populations in order to properly consider the potential of engineered nanomaterials (ENM) and fully enhance their safety. Recently, we and others have explored the vascular consequences associated with gestational nanomaterial exposure, reporting microvascular dysfunction within the uterine circulation of pregnant dams and the tail artery of fetal pups. It has been proposed (via work derived by the Barker Hypothesis) that mitochondrial dysfunction and subsequent oxidative stress mechanisms as a possible link between a hostile gestational environment and adult disease. Therefore, in this study, we exposed pregnant Sprague-Dawley rats to nanosized titanium dioxide aerosols after implantation (gestational day 6). Pups were delivered, and the progeny grew into adulthood. Microvascular reactivity, mitochondrial respiration and hydrogen peroxide production of the coronary and uterine circulations of the female offspring were evaluated. While there were no significant differences within the maternal or litter characteristics, endothelium-dependent dilation and active mechanotransduction in both coronary and uterine arterioles were significantly impaired. In addition, there was a significant reduction in maximal mitochondrial respiration (state 3) in the left ventricle and uterus. These studies demonstrate microvascular dysfunction and coincide with mitochondrial inefficiencies in both the cardiac and uterine tissues, which may represent initial evidence that prenatal ENM exposure produces microvascular impairments that persist throughout multiple developmental stages.

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“…Release of digoxin from the nanoparticles was studied under sink conditions in phosphate buffered saline (PBS) at 37°C as described previously [21,22]. In vitro drug release profiles in PBS have been previously shown to correlate well with the kinetics of in vivo therapeutic effects [18].…”

Section: Drug Releasementioning

confidence: 99%

“…The viability of BeWo cells after exposure to blank (not loaded with drug) PEGylated PLGA nanoparticles for 4, 24 and 48 h was investigated in order to determine whether the nanoparticles might affect trophoblast monolayer integrity (previous digoxin permeability studies across BeWo cell monolayers did not demonstrate any concern for the toxicity of digoxin itself to BeWo cells [22]). This was assessed by a well-established colorimetric cell proliferation, cell viability and cytotoxicity assay based on a water-soluble tetrazolium salt (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate, WST-1) (Roche Diagnostics, IN, USA).…”

Section: Cell Viabilitymentioning

confidence: 99%

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

et al. 2015

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Background: Fetal arrhythmias can lead to fetal congestive heart failure and hydrops fetalis. Digoxin (the first-line treatment) has low transplacental permeability and high risk of maternal side effects. Biodegradable digoxin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles may increase digoxin transport across BeWo b30 cell monolayers (an in vitro model of trophoblast in human placenta) by reducing the drug's interaction with P-gp. Results/methodology: The nanoparticles showed high encapsulation efficiency and sustained release over 48 h. Transport studies revealed significantly increased permeability across BeWo cell layers of digoxin-loaded nanoparticles when compared with free digoxin. P-gp inhibition also increased the permeability of digoxin, but not digoxin-loaded nanoparticles. Conclusion: This represents a novel treatment strategy for fetal cardiovascular disease which may improve maternal and fetal outcomes.

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Nanomedicine for Uterine Leiomyoma Therapy

Cited by 30 publications

References 42 publications

Statin use and uterine fibroid risk in hyperlipidemia patients: a nested case-control study

Statin use and uterine fibroid risk in hyperlipidemia patients: a nested case-control study

Microvascular and mitochondrial dysfunction in the female F1 generation after gestational TiO₂nanoparticle exposure

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

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Nanomedicine for Uterine Leiomyoma Therapy

Cited by 30 publications

References 42 publications

Statin use and uterine fibroid risk in hyperlipidemia patients: a nested case-control study

Statin use and uterine fibroid risk in hyperlipidemia patients: a nested case-control study

Microvascular and mitochondrial dysfunction in the female F1 generation after gestational TiO2nanoparticle exposure

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

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Microvascular and mitochondrial dysfunction in the female F1 generation after gestational TiO₂nanoparticle exposure