Benign prostatic hyperplasia (BPH), which is common in older men, is an enlargement of the prostate gland that may lead to bladder outlet obstruction, lower urinary tract symptoms, and reduced quality of life. Although surgery is the definitive treatment for BPH, the risks, complications, and costs of surgical intervention suggest the need for effective and safe noninvasive treatments, such as drug therapy. Ultrasound mediated-microbubbles drug delivery system is a method in which microbubbles loaded with therapeutic drugs are injected into blood vessels, and drugs are locally secreted only to target organs using ultrasound to show effects. In the current study, the effect ultrasound mediated-microbubbles drug delivery system on orchiectomy and testosterone-induced BPH animal model was investigated using rats.

To induced the BPH animal model, rats were castrated and testosterone (20 mg/kg) was injected subcutaneously once per day for 30 days. Rats in the oral drug-treated groups (tamsulosin and solifenacin) orally received each drug 3 times a weeks for a total of 12 times for 30 consecutive days after orchiectomy. Microbubble-mediated drug was administered through the femoral artery by 0.5 mL, and ultrasound was stimulated 30 minutes after administration. Microbubble-mediated drugs (tamsulosin and solifenacin loaded in microbubble) were administered once a 7 days for a total of 4 times for 30 days. Cystometry was conducted to measure voiding contraction pressure and the interval contraction time. After sacrificed, prostate tissue was collected and the prostate index was evaluated. And then, the evaluated changes in inflammation and fibrotic factors in prostate tissue, and analyzed neuronal activity in the neuronal micturition centers.

Orchiectomy and testosterone injection decreased voiding contraction pressure and the interval contraction time, suggesting BPH symptoms. Voiding contraction pressure and interval contraction time were increased in the groups that the received the ultrasound mediated-microbubbles drug groups than oral treatments groups. The prostate index decreased more in the ultrasound mediated-microbubbles drug groups. Induction of BPH increased secretion of pro-inflammatory cytokines and fibrotic factors in the bladder, and c-Fos expression in the neuronal voiding centers was enhanced by BPH induction. In contrast, expressions of pro-inflammatory cytokines, fibrotic factors, and c-Fos was suppressed by the ultrasound mediated-microbubbles drug groups to a more extent than was the case for oral treatments groups.

The conclusion of this experiment suggests the possibility that selective treatments using the ultrasound mediated-microbubbles drug delivery system the prostate is a new treatment that can overcome the limitations of oral drug use.

The effect ultrasound mediated-microbubbles drug delivery system on orchiectomy and testosterone-induced BPH animal model can overcome the limitations of oral drug use.