Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA.
BJU Int. 2011 Nov;108(10):1666-71. doi: 10.1111/j.1464-410X.2011.10185.x. Epub 2011 Mar 31.
To test the uptake efficiency of R11, a cell-permeable peptide (CPP), administered intravesically for effective drug delivery.
We used an approved in vivo model (an athymic nude mouse model) to test synthetic R11 conjugated with fluorescein isothiocyanate (FITC) at concentrations of 1 nM and 5 nM. Controls received FITC without CPP conjugation. The mice were instilled with R11 for 30 min and killed 3 or 24 h later to harvest bladders for the measurement of CPP uptake and tissue localization using frozen sections. Bladder uptake specificity was determined using the mean values of relative FITC intensity with each tissue weight.
Although the uptake of R11 varied among the mice, a 2- to 6-fold higher amount of R11 was detected in the bladder at 3 and 24 h after intravesical instillation at 1-nM or 5-nM concentrations than was detected in the bladders of each mouse control group or in other organs. Examination of tissue sections further confirmed the localization of R11 in the lamina propria of the bladder wall.
Because of its high affinity for the bladder, both systemically as reported in previous studies and after intravesical instillation as reported in the present study, R11 should be further tested in animal models as a delivery vector for agents used in treating bladder diseases.
测试 R11（一种细胞可渗透肽（CPP））的摄取效率，R11 经膀胱内给药以实现有效的药物输送。
我们使用已批准的体内模型（无胸腺裸鼠模型）来测试与荧光素异硫氰酸酯（FITC）偶联的合成 R11，浓度分别为 1 nM 和 5 nM。对照组接受未与 CPP 偶联的 FITC。将 R11 灌注小鼠 30 分钟，然后在 3 或 24 小时后处死以收获膀胱，用于使用冷冻切片测量 CPP 摄取和组织定位。使用每个组织重量的相对 FITC 强度的平均值来确定膀胱摄取的特异性。
尽管 R11 的摄取在小鼠之间有所不同，但在膀胱内灌注 1 nM 或 5 nM 浓度的 R11 后 3 小时和 24 小时，与每个小鼠对照组或其他器官中的膀胱相比，R11 的量检测到增加了 2 到 6 倍。对组织切片的检查进一步证实了 R11 在膀胱壁固有层中的定位。
由于其对膀胱的高亲和力，无论是在之前的研究中报告的全身系统中，还是在本研究中报告的膀胱内灌注后，R11 都应该在动物模型中进一步测试，作为治疗膀胱疾病的药物的递送载体。
