Department of Physiology and Biophysics, Albert Einstein College of Medicine, New York, NY, USA.
Department of Urology, Albert Einstein College of Medicine, New York, NY, USA.
J Sex Med. 2018 May;15(5):645-653. doi: 10.1016/j.jsxm.2018.03.009.
Curcumin, a naturally occurring anti-inflammatory compound, has shown promise in pre-clinical studies to treat erectile dysfunction (ED) associated with type-1 diabetes. However, poor bioavailability following oral administration limits its efficacy. The present study evaluated the potential of topical application of curcumin-loaded nanoparticles (curc-np) to treat ED in a rat model of type-2 diabetes (T2D).
Determine if topical application of curc-np treats ED in a T2D rat model and modulates expression of inflammatory markers.
Curc-np (4 mg curcumin) or blank nanoparticles were applied every 2 days for 2 weeks to the shaved abdomen of 20-week-old Zucker diabetic fatty male rats (N = 5 per group). Lean Zucker diabetic fatty male rat controls were treated with blank nanoparticles (N = 5). Penetration of nanoparticles and curcumin release were confirmed by 2-photon fluorescence microscopy and histology. Erectile function was determined by measuring intracorporal pressure (ICP) normalized to systemic blood pressure (ICP/BP) following cavernous nerve stimulation. Corporal tissue was excised and reverse transcription and quantitative polymerase chain reaction used to determine expression of the following markers: nuclear factor (NF)-κβ, NF-κβ-activating protein (Nkap), NF erythroid 2-related factor-2, Kelch-like enoyl-CoA hydratase-associated protein-1, heme oxygenase-1 (HO-1), variable coding sequence-A1, phosphodiesterase-5, endothelial and neuronal nitric oxide synthase, Ras homolog gene family member A, and Rho-associated coiled-coil containing protein kinases-1 and -2.
Erectile function by determination of ICP/BP and expression of molecular markers in corporal tissue by RT-qPCR.
Nanoparticles penetrated the abdominal epidermis and persisted in hair follicles for 24 hours. Curc-np-treated animals exhibited higher average ICP/BP than animals treated with blank nanoparticles at all levels of stimulation and this was statistically significant (P < .05) at 0.75 mA. In corporal tissue, Nkap expression decreased 60% and heme oxygenase-1 expression increased 60% in curc-np- compared to blank nanoparticle-treated animals. ICP/BP values inversely correlated with Nkap and directly correlated with HO-1 expression levels.
These studies demonstrate the potential for topical application of curc-np as a treatment for ED in T2D patients.
The T2D animal model of ED represents a more prevalent disease than the more commonly studied type-1 diabetes model. Although there is improved erectile response in curc-np-treated animals, only at the lower levels of stimulation (0.75 mA) was this significant compared to the blank nanoparticle-treated animals, suggesting more studies are needed to optimize protocols and evaluate toxicity. Topical application of curc-np to a rat model of T2D can systemically deliver curcumin, treat ED, and modulate corporal expression of inflammatory markers. Draganski A, Tar MT, Villegas G, et al. Topically Applied Curcumin-Loaded Nanoparticles Treat Erectile Dysfunction in a Rat Model of Type-2 Diabetes. J Sex Med 2018;15:645-653.
姜黄素是一种天然的抗炎化合物，在治疗 1 型糖尿病相关勃起功能障碍（ED）的临床前研究中显示出前景。然而，口服后生物利用度差限制了其疗效。本研究评估了姜黄素负载纳米粒子（curc-np）局部应用治疗 2 型糖尿病（T2D）大鼠模型 ED 的潜力。
确定 curc-np 是否可以治疗 T2D 大鼠模型中的 ED，并调节炎症标志物的表达。
20 周龄 Zucker 糖尿病肥胖雄性大鼠（每组 N = 5）腹部剃毛后每隔 2 天给予 curc-np（4 mg 姜黄素）或空白纳米粒子，共 2 周。Zucker 糖尿病肥胖雄性大鼠的瘦对照接受空白纳米粒子治疗（N = 5）。通过双光子荧光显微镜和组织学证实了纳米粒子的穿透和姜黄素的释放。通过测量海绵体内神经刺激后的腔内压力（ICP）与系统血压（ICP/BP）的比值来确定勃起功能。切除 corporal 组织，通过逆转录和定量聚合酶链反应（RT-qPCR）确定以下标志物的表达：核因子（NF）-κβ、NF-κβ激活蛋白（Nkap）、NF 红细胞 2 相关因子-2、Kelch 样烯酰辅酶 A 水合酶相关蛋白-1、血红素加氧酶-1（HO-1）、可变编码序列 A1、磷酸二酯酶-5、内皮和神经元型一氧化氮合酶、Ras 同源基因家族成员 A、Rho 相关卷曲螺旋蛋白激酶-1 和 -2。
通过 ICP/BP 确定勃起功能，通过 RT-qPCR 确定 corporal 组织中分子标志物的表达。
这些研究表明，curc-np 局部应用作为 T2D 患者 ED 的治疗方法具有潜力。
ED 的 T2D 动物模型比更常见的 1 型糖尿病模型更常见。尽管 curc-np 治疗的动物勃起反应有所改善，但与空白纳米粒子治疗的动物相比，只有在较低的刺激水平（0.75 mA）下，这才有统计学意义，这表明需要更多的研究来优化方案并评估毒性。将 curc-np 局部应用于 T2D 大鼠模型可以系统地输送姜黄素，治疗 ED，并调节 corporal 组织中炎症标志物的表达。
